Clinical Policy: Epcoritamab-bysp (Epkinly)

Reference Number: CP.PHAR.634
Effective Date: 09.01.23
Last Review Date: 08.25
Line of Business: Commercial, HIM, Medicaid

[Coding Implications](Coding Implications)
[Revision Log](Revision Log)

See Important Reminder at the end of this policy for important regulatory and legal information.

Description

Epcoritamab-bysp (Epkinly™) is a bispecific CD20-directed CD3 T-cell engager.

FDA Approved Indication(s)

Epkinly is indicated:

• For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy.*
• In combination with lenalidomide and rituximab for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL)
• As monotherapy for the treatment of adult patients with relapsed or refractory FL after two or more lines of systemic therapy.

*This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Policy/Criteria

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a. For any indication: Prescribed as monotherapy, and member has both of the following (i and ii):
i. Partial response, no response, progressive, relapsed, or refractory disease following prior systemic therapy;
ii. Member has received ≥ 2 lines of systemic therapy (see Appendix B);
b. For DLBCL, HIV-related B-cell lymphomas, and post-transplant lymphoproliferative disorders: Prescribed in combination with GemOx (gemcitabine and oxaliplatin) AND member has one of the following (i, ii, or iii):
i. Relapsed or refractory disease;
ii. Relapsed disease < 12 months after completion of first-line therapy or primary refractory disease in non-candidates for CAR T-cell therapy (includes patients who do not have access to CAR T-cell therapy);
iii. Relapsed disease > 12 months after completion of first-line therapy if no intention to proceed to transplant;
c. For classic FL: Prescribed in combination with lenalidomide and rituximab for relapsed or refractory disease.*

*Prior authorization may be required for lenalidomide and rituximab

5. Request meets one of the following (a, b, or c):
   a. All of the following (i, ii, and iii):
   i. Cycle 1 step-up doses: Dose does not exceed all the following (1, 2, 3, and 4):
   1) 0.16 mg on day 1;
   2) 0.8 mg on day 8;
   3) For FL: 3 mg on day 15;
   4) Three 4 mg/0.8 mL vials;
   ii. 48 mg per dose (one 48 mg vial; see Section V below for details on dosing schedule by cycle);
   iii. If prescribed in combination with lenalidomide and rituximab for FL, treatment does not exceed a total of 12 cycles;
   b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
   c. *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):

1. 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

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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. B-Cell Lymphomas (must meet all):

a. New dose does not exceed 48 mg per dose (one 48 mg vial; see Section V below for details on dosing schedule by cycle);
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):

1. 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
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.

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 –

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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
FL: follicular lymphoma

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.

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Appendix C: Contraindications/Boxed Warnings

• Contraindication(s): none reported
• Boxed warning(s): cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome

Appendix D: DLBCL Subtypes per the National Comprehensive Cancer Network (NCCN)

• DLBCL, NOS (FDA-approved use)
• DLBCL arising from follicular lymphoma or marginal zone lymphoma
• Primary DLBCL of the CNS
• DLBCL arising from CLL (Richter transformation)
• Follicular lymphoma grade 3B/follicular LBCL
• Intravascular LBCL
• DLBCL associated with chronic inflammation
• ALK-positive LBCL
• EBV-positive DLBCL, NOS
• T-cell/histiocyte-rich LBCL

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• LBCL with IRF4/MUM1 rearrangement
• Fibrin-associated LBCL
• Primary mediastinal LBCL
• Mediastinal gray zone lymphoma
• High-grade B-cell lymphomas with MYC and BCL2 rearrangements
• High-grade B-cell lymphomas, NOS
• High-grade B-cell lymphomas
• High-grade B-cell lymphomas with 11q aberrations
• LBCL with 11q aberration
• Primary cutaneous DLBCL, leg type

V. Dosage and Administration

VI. Product Availability

Single-dose vials for injection: 4 mg/0.8 mL, 48 mg/0.8 mL

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Coding Implications

Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Reviews, Revisions, and Approvals

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Important Reminder

This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate with standards of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan

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retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services.

Note:

For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

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