Lisocabtagene Maraleucel (Breyanzi) Form

Lisocabtagene maraleucel (Breyanzi®) is a CD19-directed genetically modified autologous T- cell immunotherapy. FDA Approved Indication(s)
Breyanzi is indicated for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have: • Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first- line chemoimmunotherapy • Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age • Relapsed or refractory disease after two or more lines of systemic therapy Limitation of use: Breyanzi is not indicated for the treatment of patients with primary central nervous system (CNS) lymphoma.
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.
All requests reviewed under this policy require medical director review. It is the policy of health plans affiliated with Centene Corporation® that Breyanzi is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Large B-Cell Lymphoma (must meet all): Only for initial treatment dose; subsequent doses will not be covered.

1. Diagnosis of one of the following LBCL (a – h); a. DLBCL; b. DLBCL transformed from one of the following (i – v): i. Follicular lymphoma;
   ii. Nodal marginal zone lymphoma; iii. Gastric mucosa-associated lymphoid tissue (MALT) lymphoma;
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   iv. Nongastric MALT Lymphoma (noncutaneous); v. Splenic marginal zone lymphoma; c. Primary mediastinal LBCL; d. Follicular lymphoma grade 3B; e. High-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 (double/triple hit lymphoma) or high-grade B-cell lymphomas, not otherwise specified; f. Monomorphic post-transplant lymphoproliferative disorders (B-cell type);
   g. HIV-related DLBCL, primary effusion lymphoma, and HHV8-positive DLBCL;
   h. T cell/histiocyte-rich LBCL and request is for second line therapy;

   2. Prescribed by or in consultation with an oncologist or hematologist;
2. Age ≥ 18 years;
3. Request is for one of the following (a, b, or c): a. Disease is refractory or member has relapsed after ≥ 2 lines of systemic therapy that includes an anti-CD20 therapy (e.g., rituximab) and one anthracycline- containing regimen (e.g., doxorubicin); b. Disease that is refractory (defined as no complete remission) to or has relapsed (defined as complete remission followed by biopsy-proven disease relapse) no more than 12 months after first-line chemoimmunotherapy that included an anti- CD20 monoclonal antibody (e.g., rituximab) and anthracycline-containing regimen (e.g., doxorubicin); c. Member is not eligible for HSCT due to comorbidities or age (see Appendix D for examples) and disease is refractory (defined as no complete remission) to or has relapsed (defined as complete remission followed by biopsy-proven disease relapse) after first-line chemoimmunotherapy that included an anti-CD20 monoclonal antibody (e.g., rituximab) and anthracycline-containing regimen (e.g., doxorubicin);
   Prior authorization may be required for rituximab
   5. Member does not have primary CNS disease;

4. Member has not previously received treatment with CAR T-cell immunotherapy (e.g., Abecma®, Carvykti™, Kymriah™, Tecartus™, Yescarta™);

   7. Breyanzi is not prescribed concurrently with other CAR T-cell immunotherapy (e.g., Abecma, Carvykti, Kymriah, Tecartus, Yescarta);
   8. Dose does not exceed 110 x 106 chimeric antigen receptor (CAR)-positive viable T cells. Approval duration: 3 months (1 dose only, with 4 doses of tocilizumab (Actemra) if requested at up to 800 mg per dose) B. Other diagnoses/indications (must meet 1 or 2):
   9. 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 Page 2 of 9

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   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

   2. 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. Large B-Cell Lymphoma
   3. Continued therapy will not be authorized as Breyanzi is indicated to be dosed one time only. Approval duration: Not applicable B. Other diagnoses/indications (must meet 1 or 2):
   4. 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
   5. 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.
      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; B. Primary CNS disease. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALC: absolute lymphocyte count CAR: chimeric antigen receptor CNS: central nervous system CRS: cytokine release syndrome DLBCL: diffuse large B-cell lymphoma FDA: Food and Drug Administration
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   HSCT: hematopoietic stem cell transplantation LBCL: large B-cell lymphoma MALT: mucosa-associated lymphoid tissue 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 First-Line Treatment Regimens RCHOP (Rituxan® (rituximab), cyclophosphamide, doxorubicin, vincristine, prednisone) RCEPP (Rituxan® (rituximab), cyclophosphamide, etoposide, prednisone, procarbazine) RCDOP (Rituxan® (rituximab), cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) DA-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) + Rituxan® (rituximab) RCEOP (Rituxan® (rituximab), cyclophosphamide, etoposide, vincristine, prednisone) RGCVP (Rituxan®, gemcitabine, cyclophosphamide, vincristine, prednisone) Second-Line Treatment Regimens Bendeka® (bendamustine) ± Rituxan® (rituximab) CEPP (cyclophosphamide, etoposide, prednisone, procarbazine) ± Rituxan® (rituximab) CEOP (cyclophosphamide, etoposide, vincristine, prednisone) ± Rituxan® (rituximab) DA-EPOCH ± Rituxan® (rituximab) GDP (gemcitabine, dexamethasone, cisplatin) ± Rituxan® (rituximab) gemcitabine, dexamethasone, carboplatin ± Rituxan® (rituximab) GemOx (gemcitabine, oxaliplatin) ± Rituxan® (rituximab) gemcitabine, vinorelbine ± Rituxan® (rituximab) lenalidomide ± Rituxan® (rituximab) Rituxan® (rituximab) DHAP (dexamethasone, cisplatin, cytarabine) ± Rituxan® (rituximab) DHAX (dexamethasone, cytarabine, oxaliplatin) ± Rituxan® (rituximab) ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) ± Rituxan® (rituximab) Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Page 4 of 9

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   Drug Name ICE (ifosfamide, carboplatin, etoposide) ± Rituxan® (rituximab) MINE (mesna, ifosfamide, mitoxantrone, etoposide) ± Rituxan® (rituximab) 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. Varies Varies Dosing Regimen Varies Dose Limit/
   Maximum Dose Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): cytokine release syndrome and neurologic toxicities Appendix D: General Information • Patients with primary CNS disease were excluded from the TRANSCEND NHL 001 trial. For primary CNS lymphoma, NCCN treatment guidelines for CNS cancers recommend a high-dose methotrexate induction based regimen or whole brain radiation therapy, and consolidation therapy with high-dose chemotherapy with stem cell rescue, high-dose cytarabine with or without etoposide, low dose whole brain radiation therapy, or continuation with monthly high-dose methotrexate-based regimen. In the TRANSCEND NHL 001 trial, three of six patients in the efficacy-evaluable set with secondary CNS lymphoma achieved a complete response. • • No prespecified threshold for blood counts, including absolute lymphocyte count, was required for enrollment in the TRANSCEND NHL 001 trial.
   • The PILOT study evaluated transplant-ineligible patients with relapsed or refractory LBCL after one line of chemoimmunotherapy. The study required at least one of the following criteria to identify patients who were not eligible for high-dose therapy and autologous HSCT: age ≥ 70 years, adjusted diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 60%; left ventricular ejection fraction (LVEF) < 50%; creatinine clearance < 60mL/min; aspartate transaminase (AST) or alanine aminotransferase (ALT) greater than two times the upper limit or normal, or Eastern Cooperative Oncology Group (ECOG) performance status of 2 (capable of all self-care but unable to carry out any work activities; up and about >50% of waking hours). V. Dosage and Administration
   Indication LBCL after two or more lines of therapy LBCL after one line of therapy Dosing Regimen Target dose: 50 to 110 x 106 CAR-positive viable T cells Target dose: 90 to 110 x 106 CAR-positive viable T cells Maximum Dose 110 x 106 CAR-positive viable T cells 110 x 106 CAR-positive viable T cells VI. Product Availability
   Single-dose 5 mL vial: frozen suspension of genetically modified autologous T-cells labeled for the specific recipient Page 5 of 9

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   VII.