BESPONSA, Inotuzumab Ozogamicin Form

Inotuzumab ozogamicin (Besponsa™) is a CD22-directed antibody-drug conjugate. FDA Approved Indication(s) Besponsa is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (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 Besponsa is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. B-Cell Precursor Acute Lymphoblastic Leukemia (must meet all):

1. Diagnosis of B-cell ALL;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. B-cell ALL is CD22 positive;
   4. Disease meets one of the following (a or b): a. Disease is relapsed or refractory;
      b. If Philadelphia chromosome-negative, both of the following (i and ii): i. Besponsa is prescribed as induction therapy;
      ii. Either age ≥ 65 years or member has substantial comorbidities;
2. Besponsa is prescribed for no more than 6 cycles total;
   6. Request meets one of the following (a or b):
      a. Dose does not exceed 1.8 mg/m2 per cycle (0.8 mg/m2 on Day 1 and 0.5 mg/m2 on Days 8 and 15); 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 (up to 6 cycles total) 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): Page 1 of 6

   CLINICAL POLICY
   Inotuzumab Ozogamicin 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. B-Cell Precursor Acute Lymphoblastic Leukemia (must meet all):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Besponsa for a covered indication and has received this medication for at least 30 days;
6. Member is responding positively to therapy;
   
   3. Member has not received ≥ 6 cycles of Besponsa;
   4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 1.8 mg/m2 per cycle (0.8 mg/m2 on Day 1 and 0.5 mg/m2 on Days 8 and 15); 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: 6 months (up to 6 cycles total) 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 6

   CLINICAL POLICY
   Inotuzumab Ozogamicin 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 ALL: acute lymphoblastic leukemia CR: complete remission CRi: complete remission with incomplete hematologic recovery Appendix B: Therapeutic Alternatives
   Not Applicable FDA: Food and Drug Administration HSCT: hematopoietic stem cell transplant Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): hepatotoxicity, including hepatic venoocclusive disease; increased risk of post-HSCT non-relapse mortality Maximum Dose 1.8 mg/m2 per cycle (0.8 mg/m2 per dose) V. Dosage and Administration
   Indication Dosing Regimen B-cell ALL If proceeding to hematopoietic stem cell transplant (HSCT): • The recommended duration is 2 cycles. A third cycle may be considered for those patients who do not achieve a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) and minimal residual disease negativity after 2 cycles.
   If not proceeding to HSCT: • Additional cycles of treatment, up to a maximum of 6 cycles, may be administered. Cycle details: Pre-medication is recommended before each dose. • For the first cycle:1.8 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Cycle 1 is 3 weeks in duration, but may be extended to 4 weeks if the patient achieves CR or CRi, and/or to allow recovery from toxicity.
   Page 3 of 6

   CLINICAL POLICY
   Inotuzumab Ozogamicin Indication Dosing Regimen Maximum Dose • For subsequent cycles:
   o In patients who achieve a CR or CRi, 1.5 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.5 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration. OR
   o In patients who do not achieve a CR or CRi, 1.8 mg/m2 per cycle given as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration.
   o Patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment.
   CR (complete remission) is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets ≥ 100 × 109/L and absolute neutrophil counts [ANC] ≥ 1 × 109/L) and resolution of any extramedullary disease. CRi (complete remission with incomplete hematologic recovery) is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets < 100 × 109/L and/or ANC < 1 × 109/L) and resolution of any extramedullary disease. VI. Product Availability
   Single-dose vial, powder for reconstitution: 0.9 mg
   VII.