BLINCYTO, Blinatumomab Form

Blinatumomab (Blincyto®) is a bispecific CD19-directed CD3 T-cell engager. FDA Approved Indication(s) Blincyto is indicated in adults and children for the treatment of: • CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) in first or second complete remission with minimal residual disease (MRD) ≥ 0.1%.This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. • Relapsed or refractory CD19-positive B-ALL.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Blincyto is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Lymphoblastic Leukemia (must meet all):

1. Diagnosis of B-ALL;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Requested as treatment for (a or b): a. B-ALL in remission but MRD-positive; b. Relapsed or refractory B-ALL (i or ii): i. Philadelphia chromosome-negative (Ph-) disease; ii. Philadelphia chromosome-positive (Ph+) disease and intolerant or refractory to at least one second- or subsequent-generation tyrosine kinase inhibitor (TKI; i.e., imatinib, Sprycel®, Tasigna®, Bosulif®, Iclusig®); Prior authorization may be required for these agents.

2. Request meets one of the following (a or b): a. Dose does not exceed 28 mcg per day; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
   Approval duration: 6 months Page 1 of 7

   CLINICAL POLICY Blinatumomab B. Other diagnoses/indications (must meet 1 or 2):

3. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
4. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Acute Lymphoblastic Leukemia (must meet all):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Blincyto for a covered indication and has received this medication for at least 30 days;
6. Member is responding positively to therapy;
   3. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 28 mcg per day; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
      Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line Page 2 of 7

   CLINICAL POLICY Blinatumomab of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key B-ALL: B-cell precursor acute lymphoblastic leukemia CR: complete remission FDA: Food and Drug Administration MRD: minimal residual disease
   NCCN: National Comprehensive Cancer Network TKI: tyrosine kinase inhibitor Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen Dose Limit/ Maximum Dose Adults: 180 mg/day Children: 100 mg/day Sprycel® (dasatinib) Ph+ ALL: Labeled use Adults: 140 mg PO QD (resistance or intolerance to prior therapy) Children and adolescents: PO QD weight-based (newly diagnosed disease) Iclusig® (ponatinib) Ph+ ALL: Labeled use 45 mg/day Adults: 45 mg PO QD (T315I-positive disease or no other TKI is indicated) Tasigna® (nilotinib) Ph+ ALL: Off-label use Bosulif® (bosutinib) Ph+ ALL: Off-label use
   imatinib (Gleevec®) Ph+ ALL: Labeled use Varies Varies 600 mg/day Adults: 600 mg PO once daily until disease progression Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. The above-referenced TKIs are NCCN recommended for PH+ ALL (category 1 or 2a). Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known hypersensitivity to blinatumomab or to any component of the product formulation • Boxed warning(s): cytokine release syndrome (CRS); neurological toxicities Page 3 of 7

   Maximum Dose 28 mcg/day 28 mcg/day CLINICAL POLICY Blinatumomab V. Dosage and Administration
   Indication Dosing Regimen B-ALL (in remission and MRD- positive) Treatment course: 1 cycle of Blincyto IV for induction followed by up to 3 additional cycles for consolidation. • Patients ≥ 45 kg receive a fixed dose o Induction cycle 1  Days 1-28: 28 mcg/day  Days 29-42: 14-day treatment-free interval B-ALL (relapsed or refractory) o Consolidation cycles 2-4  Days 1-28: 28 mcg/day  Days 29-42: 14-day treatment-free interval • Patients < 45 kg based on body surface area (BSA) o Induction cycle 1  Days 1-28: 15 mcg/m2/day  Days 29-42: 14-day treatment-free interval o Consolidation cycles 2-4  Days 1-28: 15 mcg/m2/day  Days 29-42: 14-day treatment-free interval Treatment course: 2 cycles of Blincyto IV for induction followed by 3 cycles for consolidation and up to 4 cycles of continued therapy. • Patients ≥ 45 kg receive a fixed dose o Induction cycle 1  Days 1-7: 9 mcg/day  Days 8-28: 28 mcg/day  Days 29-42: 14-day treatment-free interval o Induction cycle 2  Days 1-28: 28 mcg/day  Days 29-42: 14-day treatment-free interval o Consolidation cycles 3-5  Days 1-28: 28 mcg/day  Days 29-42: 14-day treatment-free interval o Continued therapy cycles 6-9  Days 1-28: 28 mcg/day  Days 29-84: 56-day treatment-free interval • Patients < 45 kg based on body surface area (BSA) o Induction cycle 1  Days 1-7: 5 mcg/m2/day  Days 8-28: 15 mcg/m2/day  Days 29-42: 14-day treatment-free interval o Induction cycle 2  Days 1-28: 15 mcg/m2/day  Days 29-42: 14-day treatment-free interval o Consolidation cycles 3-5  Days 1-28: 15 mcg/m2/day  Days 29-42: 14-day treatment-free interval Page 4 of 7

   CLINICAL POLICY Blinatumomab Indication Dosing Regimen Maximum Dose o Continued therapy cycles 6-9  Days 1-28: 15 mcg/m2/day  Days 29-84: 56-day treatment-free interval VI. Product Availability
   Single-dose vial for reconstitution: 35 mcg VII.