Last Review Date: 03/05/2024

Date of Origin: 05/03/2021

Dates Reviewed: 05/2021, 10/2021, 03/2022, 04/2022, 03/2023, 03/2024

1. Length of Authorization

Coverage will be provided for 6 months and may be renewed.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Zynlonta 10 mg single-dose powder for injection: 2 vials every 21 days for the first two doses followed by 1 vial every 21 days thereafter

2. Max Units (per dose and over time) [HCPCS Unit]:

• B-Cell Lymphomas

• Cycles 1 and 2: 230 billable units (17.25 mg) per each 21 day cycle

• Subsequent Cycles: 115 billable units (8.63 mg) per each 21 day cycle

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ¹

• Used as a single agent; AND
• Patient has not received prior anti-CD19 therapy, (e.g., tafasitamab, axicabtagene, tisagenlecleucel, etc.) OR patient previously received anti-CD19 therapy and re-biopsy indicates CD-19 positive disease; AND
• Patient does not have active graft-versus-host disease; AND
• Patient has not had an autologous stem cell transplant (ASCT) within 30 days or allogeneic stem cell transplant (AlloSCT) with 60 days, prior to start of therapy; AND
• Patient does not have active CNS lymphoma (includes leptomeningeal disease); AND

• Patient does not have a clinically significant active infection (e.g., Grade 3 or 4 infections); AND
• Patient does not have any clinically significant third space fluid accumulation (e.g., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath); AND

B-Cell Lymphomas † ‡ Ф ^1-4

• Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, High-Grade B-Cell Lymphoma, HIV-related DLBCL, primary effusion lymphoma, or HHV8-positive DLBCL, not otherwise specified
  • Patient has received at least two prior lines of therapy; AND
  • Patient has had no response or partial response OR has relapsed, progressive, or refractory disease
• Histologic Transformation of Indolent Lymphomas (follicular lymphoma or marginal zone lymphoma) to DLBCL ‡
  • Patient has no intention to proceed to transplant; AND
  • Patient has been previously treated with an anthracycline-based regimen; AND

• Used as additional therapy for partial response, no response, progressive, or relapsed disease following chemoimmunotherapy for histologic transformation after minimal or no prior therapy; OR
• Patient has received multiple lines of prior therapies including ≥2 chemoimmunotherapy regimens for indolent or transformed disease

• Monomorphic Post-Transplant Lymphoproliferative Disorders (PTLD) ‡
  • Used as third line and subsequent therapy for B-cell type disease; AND
  • Patient has partial response, no response, relapsed, progressive or refractory disease

† FDA Labeled Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Disease response with treatment defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe effusion and edema (e.g., pleural effusion, pericardial effusion, ascites, peripheral edema, general edema, etc.), myelosuppression (e.g., neutropenia, thrombocytopenia, anemia, etc.), serious infections, severe cutaneous reactions (e.g., photosensitivity reaction, rash, erythema, etc.), etc.

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J9359 – Injection, loncastuximab tesirine-lpyl, 0.075 mg; 1 billable unit = 0.075 mg

NDC:

• Zynlonta 10 mg single-dose powder for injection: 79952-0110-xx

7. References

1. Zynlonta [package insert]. Murray Hill, NJ; ADC Therapeutics America. October 2022. Accessed January 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) loncastuximab tesirine. National Comprehensive Cancer Network, 2024.  The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2024.
3. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for B-Cell Lymphomas Version 6.2023. National Comprehensive Cancer Network, 2023. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2024.
4. ADC Therapeutics. A Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (LOTIS-2). Available from: https://clinicaltrials.gov. NLM identifier: NCT03589469. Accessed January 17, 2024.
5. Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2021; 22:790.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A