Loncastuximab Tesirine-lpyl (Zynlonta) Form

Loncastuximab tesirine-lpyl (Zynlonta™) is a CD19-directed antibody and alkylating agent conjugate. FDA Approved Indication(s) Zynlonta is indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 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 Zynlonta is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Large B-Cell Lymphoma (must meet all):

1. Diagnosis of large B-cell lymphoma (including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma, high-grade B-cell lymphoma, AIDS- related DLBCL, primary effusion lymphoma, and HHV8-positive DLBCL not otherwise specified);

2. Prescribed by or in consultation with an oncologist or hematologist;

   3. Age ≥ 18 years;
   4. Request meets one of the following (a or b): a. Disease is refractory or member has relapsed after ≥ 2 lines of systemic therapy (see Appendix B); b. Member is not a candidate for transplant and request is for second-line therapy for partial response, no response, or progressive disease following chemoimmunotherapy in patients with histologic transformation to DLBCL (off- label); Page 1 of 6

   CLINICAL POLICY Loncastuximab Tesirine-lpyl

3. Request meets one of the following (a or b): a. Dose does not exceed 0.15 mg/kg IV every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks for subsequent cycles; 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:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer 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.
   II. Continued Therapy A. Large B-Cell Lymphoma (must meet all):
6. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Zynlonta for a covered indication and has received this medication for at least 30 days;
7. 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 0.075 mg/kg every 3 weeks; 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:
      Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

8. 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 2 of 6

   CLINICAL POLICY Loncastuximab Tesirine-lpyl 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

9. 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.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key DLBCL: diffuse large B-cell lymphoma FDA: Food and Drug Administration 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 Examples of 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, doxorubicine) + Rituxan® (rituximab) RCEOP (Rituxan® (rituximab), cyclophosphamide, etoposide, vincristine, prednisone) RGCVP (Rituxan®, gemcitabine, cyclophosphamide, vincristine, prednisone) Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Page 3 of 6

   CLINICAL POLICY Loncastuximab Tesirine-lpyl Drug Name Dosing Regimen Dose Limit/
   Maximum Dose Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Examples of 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) 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 Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Appendix C: Contraindications/Boxed Warnings None reported
   V. Dosage and Administration
   Indication Large B-cell lymphoma Dosing Regimen 0.15 mg/kg IV every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks for subsequent cycles Maximum Dose See regimen VI. Product Availability
   Lyophilized powder for reconstitution in a single-dose vial: 10 mg VII.