<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  9.6.8042.36810 -->
<!--Based on XBRL 2.1-->
<!--Created on: 2/17/2022 1:04:22 PM-->
<!--Modified on: 2/17/2022 1:04:22 PM-->
<link:linkbase xmlns="http://www.xbrl.org/2003/linkbase" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xlink="http://www.w3.org/1999/xlink" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xbrli="http://www.xbrl.org/2003/instance">
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#StatementConsolidatedBalanceSheets" roleURI="http://www.blueprintmedicines.com/role/StatementConsolidatedBalanceSheets" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#StatementConsolidatedStatementsOfOperationsAndComprehensiveIncomeLoss" roleURI="http://www.blueprintmedicines.com/role/StatementConsolidatedStatementsOfOperationsAndComprehensiveIncomeLoss" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#StatementConsolidatedStatementsOfCashFlows" roleURI="http://www.blueprintmedicines.com/role/StatementConsolidatedStatementsOfCashFlows" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#StatementConsolidatedStatementsOfCashFlowsParenthetical" roleURI="http://www.blueprintmedicines.com/role/StatementConsolidatedStatementsOfCashFlowsParenthetical" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureAcquisitionConsiderationTransferredDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureAcquisitionConsiderationTransferredDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureAcquisitionIdentifiableNetAssetsAcquiredDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureAcquisitionIdentifiableNetAssetsAcquiredDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureMarketableSecuritiesTabularDisclosureDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureMarketableSecuritiesTabularDisclosureDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureFairValueOfFinancialInstrumentsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureFairValueOfFinancialInstrumentsDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureInventoryCapitalizedDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureInventoryCapitalizedDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureInventoryBalanceSheetClassificationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureInventoryBalanceSheetClassificationDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosurePropertyAndEquipmentNetPropertyAndEquipmentAndRelatedAccumulatedDepreciationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosurePropertyAndEquipmentNetPropertyAndEquipmentAndRelatedAccumulatedDepreciationDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureAccruedExpensesDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureAccruedExpensesDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureCollaborationAndLicenseAgreementsGeneralInformationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsGeneralInformationDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureCollaborationAndLicenseAgreementsTransactionPriceDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsTransactionPriceDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureCollaborationAndLicenseAgreementsSaleOfStockDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsSaleOfStockDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureStockBasedCompensationStockBasedCompensationExpenseByTypeDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationStockBasedCompensationExpenseByTypeDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureNetIncomePerShareNetIncomeLossPerShareDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureNetIncomePerShareNetIncomeLossPerShareDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureIncomeTaxesReconciliationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureIncomeTaxesReconciliationDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureIncomeTaxesDeferredTaxAssetsAndLiabilitiesDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureIncomeTaxesDeferredTaxAssetsAndLiabilitiesDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureLeasesComponentsOfLeaseExpenseDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureLeasesComponentsOfLeaseExpenseDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureLeasesFutureMinimumLeasePaymentsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureLeasesFutureMinimumLeasePaymentsDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureLeasesTotalLeaseLiabilityDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureLeasesTotalLeaseLiabilityDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20211231.xsd#DisclosureEmployeeBenefitPlansSwitzerlandDefinedBenefitPlanDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureEmployeeBenefitPlansSwitzerlandDefinedBenefitPlanDetails" />
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementConsolidatedBalanceSheets" xlink:type="extended" xlink:title="00100 - Statement - Consolidated Balance Sheets">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity_637806998592201931" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_StockholdersEquity_637806998592201931" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockValueOutstanding" xlink:label="us-gaap_PreferredStockValueOutstanding_637806998592201931" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637806998592201931" xlink:to="us-gaap_PreferredStockValueOutstanding_637806998592201931" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockValue" xlink:label="us-gaap_CommonStockValue_637806998592201931" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637806998592201931" xlink:to="us-gaap_CommonStockValue_637806998592201931" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapital" xlink:label="us-gaap_AdditionalPaidInCapital_637806998592201931" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637806998592201931" xlink:to="us-gaap_AdditionalPaidInCapital_637806998592201931" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_637806998592201931" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637806998592201931" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_637806998592201931" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_637806998592201931" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637806998592201931" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_637806998592201931" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Liabilities" xlink:label="us-gaap_Liabilities_637806998592201931" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_Liabilities_637806998592201931" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="us-gaap_LiabilitiesCurrent_637806998592211878" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637806998592201931" xlink:to="us-gaap_LiabilitiesCurrent_637806998592211878" order="1" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="us-gaap_AccountsPayableCurrent_637806998592211878" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637806998592211878" xlink:to="us-gaap_AccountsPayableCurrent_637806998592211878" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent_637806998592211878" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637806998592211878" xlink:to="us-gaap_AccruedLiabilitiesCurrent_637806998592211878" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_637806998592211878" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637806998592211878" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_637806998592211878" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_637806998592211878" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637806998592211878" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_637806998592211878" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent_637806998592211878" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637806998592201931" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent_637806998592211878" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_637806998592211878" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637806998592201931" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_637806998592211878" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:label="us-gaap_OtherLiabilitiesNoncurrent_637806998592211878" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637806998592201931" xlink:to="us-gaap_OtherLiabilitiesNoncurrent_637806998592211878" order="4" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Assets" xlink:label="us-gaap_Assets" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="us-gaap_AssetsCurrent_637806998592221863" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsCurrent_637806998592221863" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_637806998592221863" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637806998592221863" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_637806998592221863" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_UnbilledReceivablesIncludingReimbursableCostsCurrent" xlink:label="bpmc_UnbilledReceivablesIncludingReimbursableCostsCurrent_637806998592221863" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637806998592221863" xlink:to="bpmc_UnbilledReceivablesIncludingReimbursableCostsCurrent_637806998592221863" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_637806998592221863" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637806998592221863" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_637806998592221863" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet_637806998592221863" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637806998592221863" xlink:to="us-gaap_InventoryNet_637806998592221863" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent" xlink:label="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_637806998592231923" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637806998592221863" xlink:to="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_637806998592231923" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:label="us-gaap_AccountsReceivableNetCurrent_637806998592231923" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637806998592221863" xlink:to="us-gaap_AccountsReceivableNetCurrent_637806998592231923" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_637806998592231923" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_637806998592231923" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_637806998592231923" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_637806998592231923" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_637806998592231923" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset_637806998592231923" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="us-gaap_OtherAssetsNoncurrent_637806998592231923" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OtherAssetsNoncurrent_637806998592231923" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashNoncurrent" xlink:label="us-gaap_RestrictedCashNoncurrent_637806998592231923" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_RestrictedCashNoncurrent_637806998592231923" order="6" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementConsolidatedStatementsOfOperationsAndComprehensiveIncomeLoss" xlink:type="extended" xlink:title="00200 - Statement - Consolidated Statements of Operations and Comprehensive Income (Loss)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss_637806998592241868" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_NetIncomeLoss_637806998592241868" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637806998592241868" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_637806998592241868" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637806998592241868" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_637806998592241868" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637806998592241868" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_637806998592241868" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostsAndExpenses" xlink:label="us-gaap_CostsAndExpenses_637806998592241868" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637806998592241868" xlink:to="us-gaap_CostsAndExpenses_637806998592241868" order="2" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="us-gaap_CostOfGoodsAndServicesSold_637806998592241868" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostsAndExpenses_637806998592241868" xlink:to="us-gaap_CostOfGoodsAndServicesSold_637806998592241868" order="1" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense_637806998592251852" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostsAndExpenses_637806998592241868" xlink:to="us-gaap_ResearchAndDevelopmentExpense_637806998592251852" order="2" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense_637806998592251852" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostsAndExpenses_637806998592241868" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpense_637806998592251852" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborationProfitLossSharing" xlink:label="bpmc_CollaborationProfitLossSharing_637806998592251852" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostsAndExpenses_637806998592241868" xlink:to="bpmc_CollaborationProfitLossSharing_637806998592251852" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NonoperatingIncomeExpense" xlink:label="us-gaap_NonoperatingIncomeExpense_637806998592251852" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637806998592241868" xlink:to="us-gaap_NonoperatingIncomeExpense_637806998592251852" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_637806998592251852" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense_637806998592251852" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_637806998592251852" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestIncomeExpenseNet" xlink:label="us-gaap_InterestIncomeExpenseNet_637806998592251852" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense_637806998592251852" xlink:to="us-gaap_InterestIncomeExpenseNet_637806998592251852" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="us-gaap_IncomeTaxExpenseBenefit_637806998592251852" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_637806998592241868" xlink:to="us-gaap_IncomeTaxExpenseBenefit_637806998592251852" order="2" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_637806998592251852" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_637806998592251852" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_637806998592261850" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_637806998592261850" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeDefinedBenefitPlansNetUnamortizedGainLossArisingDuringPeriodNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeDefinedBenefitPlansNetUnamortizedGainLossArisingDuringPeriodNetOfTax_637806998592261850" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeDefinedBenefitPlansNetUnamortizedGainLossArisingDuringPeriodNetOfTax_637806998592261850" order="4" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementConsolidatedStatementsOfCashFlows" xlink:type="extended" xlink:title="00400 - Statement - Consolidated Statements of Cash Flows">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" order="1" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProfitLoss" xlink:label="us-gaap_ProfitLoss_637806998592261850" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_ProfitLoss_637806998592261850" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization" xlink:label="us-gaap_DepreciationDepletionAndAmortization_637806998592261850" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_DepreciationDepletionAndAmortization_637806998592261850" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_LeaseRightOfUseAssetAmortization" xlink:label="bpmc_LeaseRightOfUseAssetAmortization_637806998592261850" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="bpmc_LeaseRightOfUseAssetAmortization_637806998592261850" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="us-gaap_ShareBasedCompensation_637806998592261850" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_ShareBasedCompensation_637806998592261850" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_AcquiredProductiveAssetsInProcessResearchAndDevelopmentExpensed" xlink:label="bpmc_AcquiredProductiveAssetsInProcessResearchAndDevelopmentExpensed_637806998592271865" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="bpmc_AcquiredProductiveAssetsInProcessResearchAndDevelopmentExpensed_637806998592271865" order="5" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_AccretionOfPremiumsAndDiscountsOnInvestments" xlink:label="bpmc_AccretionOfPremiumsAndDiscountsOnInvestments_637806998592271865" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="bpmc_AccretionOfPremiumsAndDiscountsOnInvestments_637806998592271865" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherOperatingActivitiesCashFlowStatement" xlink:label="us-gaap_OtherOperatingActivitiesCashFlowStatement_637806998592271865" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_OtherOperatingActivitiesCashFlowStatement_637806998592271865" order="7" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable_637806998592271865" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayable_637806998592271865" order="8" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_IncreaseDecreaseInCustomerAssets" xlink:label="bpmc_IncreaseDecreaseInCustomerAssets_637806998592271865" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="bpmc_IncreaseDecreaseInCustomerAssets_637806998592271865" order="9" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="us-gaap_IncreaseDecreaseInInventories_637806998592271865" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_IncreaseDecreaseInInventories_637806998592271865" order="10" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:label="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_637806998592281942" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_637806998592281942" order="11" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable" xlink:label="us-gaap_IncreaseDecreaseInAccountsReceivable_637806998592281942" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_IncreaseDecreaseInAccountsReceivable_637806998592281942" order="12" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherNoncurrentAssets" xlink:label="us-gaap_IncreaseDecreaseInOtherNoncurrentAssets_637806998592281942" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_IncreaseDecreaseInOtherNoncurrentAssets_637806998592281942" order="13" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities" xlink:label="us-gaap_IncreaseDecreaseInAccruedLiabilities_637806998592281942" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_IncreaseDecreaseInAccruedLiabilities_637806998592281942" order="14" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability" xlink:label="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_637806998592281942" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_637806998592281942" order="15" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOperatingLeaseLiability" xlink:label="us-gaap_IncreaseDecreaseInOperatingLeaseLiability_637806998592281942" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637806998592261850" xlink:to="us-gaap_IncreaseDecreaseInOperatingLeaseLiability_637806998592281942" order="16" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_637806998592281942" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_637806998592281942" order="2" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_637806998592291867" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637806998592281942" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_637806998592291867" order="1" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireIntangibleAssets" xlink:label="us-gaap_PaymentsToAcquireIntangibleAssets_637806998592291867" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637806998592281942" xlink:to="us-gaap_PaymentsToAcquireIntangibleAssets_637806998592291867" order="2" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_637806998592291867" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637806998592281942" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_637806998592291867" order="3" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities" xlink:label="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_637806998592291867" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637806998592281942" xlink:to="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_637806998592291867" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_637806998592291867" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_637806998592291867" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_ProceedsFromIssuanceOfCommonStockNetOfUnderwritingDiscountsCommissionsAndOfferingExpenses" xlink:label="bpmc_ProceedsFromIssuanceOfCommonStockNetOfUnderwritingDiscountsCommissionsAndOfferingExpenses_637806998592291867" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637806998592291867" xlink:to="bpmc_ProceedsFromIssuanceOfCommonStockNetOfUnderwritingDiscountsCommissionsAndOfferingExpenses_637806998592291867" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_NetProceedsFromStockOptionExercisesAndEmployeeStockPurchasePlan" xlink:label="bpmc_NetProceedsFromStockOptionExercisesAndEmployeeStockPurchasePlan_637806998592301857" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637806998592291867" xlink:to="bpmc_NetProceedsFromStockOptionExercisesAndEmployeeStockPurchasePlan_637806998592301857" order="2" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfPrivatePlacement" xlink:label="us-gaap_ProceedsFromIssuanceOfPrivatePlacement_637806998592301857" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637806998592291867" xlink:to="us-gaap_ProceedsFromIssuanceOfPrivatePlacement_637806998592301857" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromPaymentsForOtherFinancingActivities" xlink:label="us-gaap_ProceedsFromPaymentsForOtherFinancingActivities_637806998592301857" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637806998592291867" xlink:to="us-gaap_ProceedsFromPaymentsForOtherFinancingActivities_637806998592301857" order="4" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementConsolidatedStatementsOfCashFlowsParenthetical" xlink:type="extended" xlink:title="00405 - Statement - Consolidated Statements of Cash Flows (Parenthetical)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_637806998592301857" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_637806998592301857" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashCurrent" xlink:label="us-gaap_RestrictedCashCurrent_637806998592311983" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_RestrictedCashCurrent_637806998592311983" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashNoncurrent" xlink:label="us-gaap_RestrictedCashNoncurrent_637806998592311983" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_RestrictedCashNoncurrent_637806998592311983" order="3" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureAcquisitionConsiderationTransferredDetails" xlink:type="extended" xlink:title="40302 - Disclosure - Acquisition - Consideration Transferred (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetAcquisitionConsiderationTransferred" xlink:label="us-gaap_AssetAcquisitionConsiderationTransferred" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_AssetAcquisitionConsiderationTransferredUpfrontPayment" xlink:label="bpmc_AssetAcquisitionConsiderationTransferredUpfrontPayment_637806998592311983" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetAcquisitionConsiderationTransferred" xlink:to="bpmc_AssetAcquisitionConsiderationTransferredUpfrontPayment_637806998592311983" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_AssetAcquisitionConsiderationTransferredAdjustmentsNetIndebtednessTransactionExpensesAndOtherAdjustments" xlink:label="bpmc_AssetAcquisitionConsiderationTransferredAdjustmentsNetIndebtednessTransactionExpensesAndOtherAdjustments_637806998592311983" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetAcquisitionConsiderationTransferred" xlink:to="bpmc_AssetAcquisitionConsiderationTransferredAdjustmentsNetIndebtednessTransactionExpensesAndOtherAdjustments_637806998592311983" order="2" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureAcquisitionIdentifiableNetAssetsAcquiredDetails" xlink:type="extended" xlink:title="40305 - Disclosure - Acquisition - Identifiable Net Assets Acquired (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsNet" xlink:label="us-gaap_AssetsNet" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_AssetAcquisitionRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesNet" xlink:label="bpmc_AssetAcquisitionRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesNet_637806998592311983" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNet" xlink:to="bpmc_AssetAcquisitionRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesNet_637806998592311983" order="1" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwill" xlink:label="us-gaap_IntangibleAssetsNetExcludingGoodwill_637806998592311983" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNet" xlink:to="us-gaap_IntangibleAssetsNetExcludingGoodwill_637806998592311983" order="2" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureMarketableSecuritiesTabularDisclosureDetails" xlink:type="extended" xlink:title="40401 - Disclosure - Marketable Securities - Tabular Disclosure (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_637806998592321873" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_637806998592321873" order="1" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_637806998592321873" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_637806998592321873" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637806998592321873" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637806998592321873" order="3" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureFairValueOfFinancialInstrumentsDetails" xlink:type="extended" xlink:title="40501 - Disclosure - Fair Value of Financial Instruments (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="us-gaap_AssetsFairValueDisclosure" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637806998592321873" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637806998592321873" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure_637806998592321873" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure_637806998592321873" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureInventoryCapitalizedDetails" xlink:type="extended" xlink:title="40701 - Disclosure - Inventory - Capitalized (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_InventoryCurrentAndNoncurrentNet" xlink:label="bpmc_InventoryCurrentAndNoncurrentNet" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_InventoryCurrentAndNoncurrentWorkInProcessNetOfReserves" xlink:label="bpmc_InventoryCurrentAndNoncurrentWorkInProcessNetOfReserves_637806998592321873" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_InventoryCurrentAndNoncurrentNet" xlink:to="bpmc_InventoryCurrentAndNoncurrentWorkInProcessNetOfReserves_637806998592321873" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_InventoryCurrentAndNoncurrentFinishedGoodsNetOfReserves" xlink:label="bpmc_InventoryCurrentAndNoncurrentFinishedGoodsNetOfReserves_637806998592331858" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_InventoryCurrentAndNoncurrentNet" xlink:to="bpmc_InventoryCurrentAndNoncurrentFinishedGoodsNetOfReserves_637806998592331858" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_InventoryCurrentAndNoncurrentRawMaterialsNetOfReserves" xlink:label="bpmc_InventoryCurrentAndNoncurrentRawMaterialsNetOfReserves_637806998592331858" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_InventoryCurrentAndNoncurrentNet" xlink:to="bpmc_InventoryCurrentAndNoncurrentRawMaterialsNetOfReserves_637806998592331858" order="3" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureInventoryBalanceSheetClassificationDetails" xlink:type="extended" xlink:title="40702 - Disclosure - Inventory - Balance Sheet Classification (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_InventoryCurrentAndNoncurrentNet" xlink:label="bpmc_InventoryCurrentAndNoncurrentNet" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet_637806998592331858" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_InventoryCurrentAndNoncurrentNet" xlink:to="us-gaap_InventoryNet_637806998592331858" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNoncurrent" xlink:label="us-gaap_InventoryNoncurrent_637806998592331858" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_InventoryCurrentAndNoncurrentNet" xlink:to="us-gaap_InventoryNoncurrent_637806998592331858" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosurePropertyAndEquipmentNetPropertyAndEquipmentAndRelatedAccumulatedDepreciationDetails" xlink:type="extended" xlink:title="40902 - Disclosure - Property and Equipment, Net - Property and Equipment and Related Accumulated Depreciation (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_635902680813050767" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" xlink:label="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_637806998592331858" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PropertyPlantAndEquipmentNet_635902680813050767" xlink:to="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_637806998592331858" order="1" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentGross" xlink:label="us-gaap_PropertyPlantAndEquipmentGross_637806998592331858" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PropertyPlantAndEquipmentNet_635902680813050767" xlink:to="us-gaap_PropertyPlantAndEquipmentGross_637806998592331858" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureAccruedExpensesDetails" xlink:type="extended" xlink:title="41001 - Disclosure - Accrued Expenses (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_ExternalResearchDevelopmentAndCommercialContractCostsCurrent" xlink:label="bpmc_ExternalResearchDevelopmentAndCommercialContractCostsCurrent_637806998592342094" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="bpmc_ExternalResearchDevelopmentAndCommercialContractCostsCurrent_637806998592342094" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_AccruedContractWithCustomerAssetAccumulatedAllowanceForCreditLoss" xlink:label="bpmc_AccruedContractWithCustomerAssetAccumulatedAllowanceForCreditLoss_637806998592342094" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="bpmc_AccruedContractWithCustomerAssetAccumulatedAllowanceForCreditLoss_637806998592342094" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent_637806998592342094" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent_637806998592342094" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedProfessionalFeesCurrent" xlink:label="us-gaap_AccruedProfessionalFeesCurrent_637806998592342094" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedProfessionalFeesCurrent_637806998592342094" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAccruedLiabilitiesCurrent" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent_637806998592342094" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_OtherAccruedLiabilitiesCurrent_637806998592342094" order="5" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsGeneralInformationDetails" xlink:type="extended" xlink:title="41101 - Disclosure - Collaboration and License Agreements - General Information (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" xlink:label="bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementMilestonesDevelopmentAndRegulatoryMilestonesContingentPaymentsEligibleToReceive" xlink:label="bpmc_CollaborativeArrangementMilestonesDevelopmentAndRegulatoryMilestonesContingentPaymentsEligibleToReceive_637806998592351870" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" xlink:to="bpmc_CollaborativeArrangementMilestonesDevelopmentAndRegulatoryMilestonesContingentPaymentsEligibleToReceive_637806998592351870" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementMilestonesSalesBasedMilestonesContingentPaymentsEligibleToReceive" xlink:label="bpmc_CollaborativeArrangementMilestonesSalesBasedMilestonesContingentPaymentsEligibleToReceive_637806998592351870" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" xlink:to="bpmc_CollaborativeArrangementMilestonesSalesBasedMilestonesContingentPaymentsEligibleToReceive_637806998592351870" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsTransactionPriceDetails" xlink:type="extended" xlink:title="41102 - Disclosure - Collaboration and License Agreements - Transaction Price (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementTransactionPrice" xlink:label="bpmc_CollaborativeArrangementTransactionPrice" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementTransactionPriceUpfrontPayment" xlink:label="bpmc_CollaborativeArrangementTransactionPriceUpfrontPayment_637806998592351870" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceUpfrontPayment_637806998592351870" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementTransactionPriceStockIssuedPremiumOnSaleOfStockToCounterparty" xlink:label="bpmc_CollaborativeArrangementTransactionPriceStockIssuedPremiumOnSaleOfStockToCounterparty_637806998592351870" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceStockIssuedPremiumOnSaleOfStockToCounterparty_637806998592351870" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivable" xlink:label="bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivable_637806998592351870" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivable_637806998592351870" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivedAndReceivable" xlink:label="bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivedAndReceivable_637806998592351870" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivedAndReceivable_637806998592351870" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyExistingManufacturingInventory" xlink:label="bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyExistingManufacturingInventory_637806998592351870" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyExistingManufacturingInventory_637806998592351870" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyInProcessManufacturingInventory" xlink:label="bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyInProcessManufacturingInventory_637806998592351870" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyInProcessManufacturingInventory_637806998592351870" order="6" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsSaleOfStockDetails" xlink:type="extended" xlink:title="41103 - Disclosure - Collaboration and License Agreements - Sale of Stock (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" xlink:label="bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues_637806998592361946" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues_637806998592361946" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_StockIssuedDuringPeriodValueNewIssuesPremium" xlink:label="bpmc_StockIssuedDuringPeriodValueNewIssuesPremium_637806998592361946" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" xlink:to="bpmc_StockIssuedDuringPeriodValueNewIssuesPremium_637806998592361946" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationStockBasedCompensationExpenseByTypeDetails" xlink:type="extended" xlink:title="41304 - Disclosure - Stock-based Compensation - Stock-based Compensation Expense - By Type (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_637806998592361946" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_637806998592361946" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense_637806998592361946" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense_637806998592361946" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureNetIncomePerShareNetIncomeLossPerShareDetails" xlink:type="extended" xlink:title="41401 - Disclosure - Net Income Per Share - Net Income (Loss) Per Share (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:label="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic" xlink:label="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_637806998592371862" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:to="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_637806998592371862" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss_637806998592371862" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_637806998592371862" xlink:to="us-gaap_NetIncomeLoss_637806998592371862" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_637806998592371862" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_637806998592371862" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:label="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_637806998592371862" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_637806998592371862" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureIncomeTaxesReconciliationDetails" xlink:type="extended" xlink:title="41501 - Disclosure - Income Taxes - Reconciliation (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:label="us-gaap_EffectiveIncomeTaxRateContinuingOperations" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_637806998592371862" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_637806998592371862" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpense" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpense_637806998592381650" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpense_637806998592381650" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseResearchAndDevelopment" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseResearchAndDevelopment_637806998592381650" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseResearchAndDevelopment_637806998592381650" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationTaxCreditsResearch" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationTaxCreditsResearch_637806998592381650" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationTaxCreditsResearch_637806998592381650" order="4" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_EffectiveIncomeTaxRateReconciliationTaxCreditGeneralBusinessPercent" xlink:label="bpmc_EffectiveIncomeTaxRateReconciliationTaxCreditGeneralBusinessPercent_637806998592381650" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="bpmc_EffectiveIncomeTaxRateReconciliationTaxCreditGeneralBusinessPercent_637806998592381650" order="5" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes_637806998592381650" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes_637806998592381650" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments_637806998592381650" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments_637806998592381650" order="7" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential_637806998592381650" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential_637806998592381650" order="8" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate_637806998592381650" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate_637806998592381650" order="9" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationTaxCreditsForeign" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationTaxCreditsForeign_637806998592381650" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationTaxCreditsForeign_637806998592381650" order="10" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance_637806998592391889" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance_637806998592391889" order="11" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureIncomeTaxesDeferredTaxAssetsAndLiabilitiesDetails" xlink:type="extended" xlink:title="41502 - Disclosure - Income Taxes - Deferred Tax Assets and Liabilities (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsLiabilitiesNet" xlink:label="us-gaap_DeferredTaxAssetsLiabilitiesNet" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsGross" xlink:label="us-gaap_DeferredTaxAssetsGross_637806998592391889" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsLiabilitiesNet" xlink:to="us-gaap_DeferredTaxAssetsGross_637806998592391889" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsOperatingLossCarryforwards" xlink:label="us-gaap_DeferredTaxAssetsOperatingLossCarryforwards_637806998592391889" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross_637806998592391889" xlink:to="us-gaap_DeferredTaxAssetsOperatingLossCarryforwards_637806998592391889" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsResearch" xlink:label="us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsResearch_637806998592391889" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross_637806998592391889" xlink:to="us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsResearch_637806998592391889" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsGeneralBusiness" xlink:label="us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsGeneralBusiness_637806998592391889" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross_637806998592391889" xlink:to="us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsGeneralBusiness_637806998592391889" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilities" xlink:label="us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilities_637806998592391889" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross_637806998592391889" xlink:to="us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilities_637806998592391889" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsDeferredIncome" xlink:label="us-gaap_DeferredTaxAssetsDeferredIncome_637806998592401991" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross_637806998592391889" xlink:to="us-gaap_DeferredTaxAssetsDeferredIncome_637806998592401991" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsDeferredRent" xlink:label="us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsDeferredRent_637806998592401991" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross_637806998592391889" xlink:to="us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsDeferredRent_637806998592401991" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets" xlink:label="us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets_637806998592401991" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross_637806998592391889" xlink:to="us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets_637806998592401991" order="7" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetInterestCarryforward" xlink:label="us-gaap_DeferredTaxAssetInterestCarryforward_637806998592401991" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross_637806998592391889" xlink:to="us-gaap_DeferredTaxAssetInterestCarryforward_637806998592401991" order="8" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment" xlink:label="us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment_637806998592401991" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsLiabilitiesNet" xlink:to="us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment_637806998592401991" order="2" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20211231.xsd#bpmc_DeferredTaxLiabilitiesRightOfUseAssets" xlink:label="bpmc_DeferredTaxLiabilitiesRightOfUseAssets_637806998592401991" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsLiabilitiesNet" xlink:to="bpmc_DeferredTaxLiabilitiesRightOfUseAssets_637806998592401991" order="3" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxLiabilitiesDeferredExpense" xlink:label="us-gaap_DeferredTaxLiabilitiesDeferredExpense_637806998592401991" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsLiabilitiesNet" xlink:to="us-gaap_DeferredTaxLiabilitiesDeferredExpense_637806998592401991" order="4" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxLiabilitiesPrepaidExpenses" xlink:label="us-gaap_DeferredTaxLiabilitiesPrepaidExpenses_637806998592411887" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsLiabilitiesNet" xlink:to="us-gaap_DeferredTaxLiabilitiesPrepaidExpenses_637806998592411887" order="5" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsValuationAllowance" xlink:label="us-gaap_DeferredTaxAssetsValuationAllowance_637806998592411887" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsLiabilitiesNet" xlink:to="us-gaap_DeferredTaxAssetsValuationAllowance_637806998592411887" order="6" use="optional" weight="-1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureLeasesComponentsOfLeaseExpenseDetails" xlink:type="extended" xlink:title="41602 - Disclosure - Leases - Components of Lease Expense (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LeaseCost" xlink:label="us-gaap_LeaseCost" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseCost" xlink:label="us-gaap_OperatingLeaseCost_637806998592411887" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LeaseCost" xlink:to="us-gaap_OperatingLeaseCost_637806998592411887" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubleaseIncome" xlink:label="us-gaap_SubleaseIncome_637806998592411887" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LeaseCost" xlink:to="us-gaap_SubleaseIncome_637806998592411887" order="2" use="optional" weight="-1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureLeasesFutureMinimumLeasePaymentsDetails" xlink:type="extended" xlink:title="41605 - Disclosure - Leases - Future Minimum Lease Payments (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_637806998592411887" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_637806998592411887" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_637806998592421848" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_637806998592421848" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_637806998592421848" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_637806998592421848" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_637806998592421848" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_637806998592421848" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_637806998592421848" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_637806998592421848" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_637806998592421848" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_637806998592421848" order="6" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureLeasesTotalLeaseLiabilityDetails" xlink:type="extended" xlink:title="41606 - Disclosure - Leases - Total Lease Liability (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_637806998592421848" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_637806998592421848" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="us-gaap_OperatingLeaseLiability_637806998592421848" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_OperatingLeaseLiability_637806998592421848" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureEmployeeBenefitPlansSwitzerlandDefinedBenefitPlanDetails" xlink:type="extended" xlink:title="41702 - Disclosure - Employee Benefit Plans - Switzerland Defined Benefit Plan (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanFundedStatusOfPlan" xlink:label="us-gaap_DefinedBenefitPlanFundedStatusOfPlan" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanPensionPlansWithAccumulatedBenefitObligationsInExcessOfPlanAssetsAggregateFairValueOfPlanAssets" xlink:label="us-gaap_DefinedBenefitPlanPensionPlansWithAccumulatedBenefitObligationsInExcessOfPlanAssetsAggregateFairValueOfPlanAssets_637806998592431863" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DefinedBenefitPlanFundedStatusOfPlan" xlink:to="us-gaap_DefinedBenefitPlanPensionPlansWithAccumulatedBenefitObligationsInExcessOfPlanAssetsAggregateFairValueOfPlanAssets_637806998592431863" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanPensionPlansWithAccumulatedBenefitObligationsInExcessOfPlanAssetsAggregateProjectedBenefitObligation" xlink:label="us-gaap_DefinedBenefitPlanPensionPlansWithAccumulatedBenefitObligationsInExcessOfPlanAssetsAggregateProjectedBenefitObligation_637806998592431863" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DefinedBenefitPlanFundedStatusOfPlan" xlink:to="us-gaap_DefinedBenefitPlanPensionPlansWithAccumulatedBenefitObligationsInExcessOfPlanAssetsAggregateProjectedBenefitObligation_637806998592431863" order="2" use="optional" weight="-1" />
  </calculationLink>
</link:linkbase>
