CurrentCentenePolicy CP PHAR.539

Loncastuximab Tesirine-Ipyl (Zynlonta)

Clinical coverage policy for loncastuximab tesirine-Ipyl (Zynlonta) for treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including described subtypes; includes initial and continued therapy criteria, dosing, approval durations, coding, and formulary/off-label referral guidance for Centene lines of business (Commercial, HIM, Medicaid).

Policy Summary

PayerCentene

PolicyLoncastuximab Tesirine-Ipyl (Zynlonta)

Policy CodePolicy CP PHAR.539

Change TypeAnnual reviews with revisions and clarifications (2022–2025)

Effective Date09.01.21

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, or other clinical information) supporting that member meets all approval criteria including diagnosis, prior therapies, transplant candidacy status, and dosing.

POLICY UPDATE CHANGES

3Q 2024 annual review: revised language from AIDS-related DLBCL to HIV-related DLBCL; added PTLD and histologic transformation of indolent lymphomas related to DLBCL as examples; updated Appendix B and references.

3Q 2022 annual review: added use in AIDS-related (later aligned to HIV-related) DLBCL, primary effusion lymphoma, and HHV8-positive DLBCL NOS; added off-label second-line transplant-ineligible use; clarified Commercial approval duration is the longer of 6 months or member renewal date; updated HCPCS code.

3Q 2023 annual review: added requirement that Zynlonta be prescribed as a single agent per NCCN.

3Q 2025 annual review: no significant changes; references reviewed and updated.

1FDA-approved indication

≥2Required prior systemic therapy lines

Coverage Summary

Scope: Clinical coverage policy for loncastuximab tesirine-Ipyl (Zynlonta) for treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including described subtypes. Coverage stance: covered_with_criteria. Approval context: Zynlonta is indicated under accelerated approval for adults with relapsed or refractory large B-cell lymphoma after ≥ 2 prior systemic therapies (including DLBCL and specified subtypes). Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s) to support ongoing approval.

Key thresholds

Prior lines of systemic therapy≥ 2 lines

Age≥ 18 years

Initial dosing limit0.15 mg/kg IV every 3 weeks for 2 cycles

Maintenance dosing limit0.075 mg/kg IV every 3 weeks

Minimum exposure before continuation≥ 30 days

Initial Therapy Criteria - Large B‑Cell Lymphoma

Initial Therapy Criteria - Other Diagnoses/Indications

Continuation Therapy Criteria

Diagnoses / Indications Not Authorized

Diagnoses/Indications Not Authorized

Diagnoses/Indications Not Authorized: Non-FDA approved indications not addressed in this policy are not authorized unless sufficient documentation of efficacy and safety is provided according to off-label use policies (CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, CP.PMN.53 for Medicaid) or evidence of coverage documents

Applicable Codes

HCPCS codes (informational)HCPCS

J9359

Injection, loncastuximab tesirine-lpyl, 0.075 mg

Provider Actions & Billing

Prior Authorization

Documentation required for approval

Providers must submit documentation supporting that the member meets all approval criteria. Required documentation should demonstrate the diagnosis, prior systemic therapies, transplant candidacy status (or reason not a candidate), and the dosing regimen requested (initial or current dose and schedule). Acceptable examples include office chart notes, laboratory results, and other clinical information.

Affected code: J9359
Examples of acceptable documentation: office chart notes, lab results, other clinical information

Documentation Required

Support evidence for off-label use or dose increase

For off-label second-line use in transplant-ineligible patients or for requests to increase the dose, the prescriber must submit supporting practice guidelines or peer‑reviewed literature that justify the regimen or dose. The prescriber is responsible for providing the cited guideline or literature when requesting authorization.

Clinical Evidence & Guidance

Key evidence sources: FDA Prescribing Information — Zynlonta prescribing information (ADC Therapeutics America); October 2022. NCCN sources: NCCN B-Cell Lymphomas Compendium and Drugs & Biologics Compendium (references reviewed through 2025). Note: the FDA indication is under accelerated approval based on overall response rate, and continued approval may require confirmatory trials verifying clinical benefit.

Background & Definitions

Background: Zynlonta (loncastuximab tesirine-Ipyl) is a CD19-directed antibody-drug conjugate. It is indicated under accelerated approval for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy (including DLBCL and specified subtypes). The accelerated approval was granted based on overall response rate; continued approval may be contingent on verification and description of clinical benefit in confirmatory trial(s). The FDA-approved dosing regimen for large B-cell lymphoma is 0.15 mg/kg IV every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks.

Definitions: DLBCL — Diffuse large B-cell lymphoma. PTLD — Post-transplant lymphoproliferative disorders.

Revision History

05.03.223Q 2022 annual review

3Q 2022 annual review: per NCCN compendium, added use in AIDS-related (later aligned to HIV-related) DLBCL, primary effusion lymphoma, and HHV8-positive DLBCL not otherwise specified; added off-label second-line transplant-ineligible use for histologic transformation to DLBCL; clarified Commercial approval duration is the longer of 6 months or member renewal date; updated HCPCS code; references reviewed and updated. P&T Approval Date = 08.22

04.07.233Q 2023 annual review

3Q 2023 annual review: added requirement that Zynlonta be prescribed as a single agent per NCCN; references reviewed and updated. P&T Approval Date = 08.23

05.06.243Q 2024 annual review