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Last Review Date: 06/04/2024

Date of Origin: 03/01/2021

Dates Reviewed: 03/2021, 07/2021, 10/2021, 11/2021, 08/2022, 11/2023, 04/2024, 06/2024

1. Length of Authorization

Coverage will be provided for one treatment course (1 dose of Breyanzi) and may not be renewed.

2. Dosing Limits

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

• 1 carton (1 to 4 vials) of up to 110 million autologous anti-CD19 CAR-positive viable T-cells

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

• 1 billable unit (1 infusion of up to 110 million autologous anti-CD19 CAR-positive viable T-cells)

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age (unless otherwise specified); AND
• Patient does not have a clinically significant active systemic infection or inflammatory disorder; AND
• Patient has not received live vaccines within 6 weeks prior to the start of lymphodepleting chemotherapy, and will not receive live vaccines during lisocabtagene maraleucel treatment and until immune recovery following treatment; AND
• Patient has been screened for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines prior to collection of cells (leukapheresis); AND
• Prophylaxis for infection will be followed according to standard institutional guidelines; AND
• Healthcare facility must be enrolled in and comply with the requirements of the BREYANZI REMS Program; AND
• Patient has not received prior CAR-T therapy; AND
• Patient has not received other anti-CD19 therapy (e.g., tafasitamab, blinatumomab, loncastuximab tesirine, etc.) OR patient previously received other anti-CD19 therapy and re-biopsy indicates CD-19 positive disease; AND
• Used as single agent therapy (not applicable to lymphodepleting or bridging chemotherapy while awaiting manufacture); AND
• Patient does not have primary central nervous system lymphoma; AND

B-Cell Lymphomas † ‡ Ф ^1,2,7,9-11

• Patient has diffuse large B cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma (FL) grade 3b, HIV-related B-cell lymphoma (i.e., HIV-related DLBCL, primary effusion lymphoma, and HHV8-positive DLBCL, not otherwise specified), or monomorphic post-transplant lymphoproliferative disorder (PTLD) (B-cell type); AND
  • Used for primary refractory disease (partial response, no response, or progression) or relapsed disease within 12 months after completion of first-line therapy; OR
  • Used for relapsed or refractory disease after first-line chemoimmunotherapy in patients NOT eligible for hematopoietic stem cell transplantation (HSCT) (Note: Excludes HIV-related B-cell lymphoma and monomorphic PTLD); OR
  • Used as second-line therapy for relapsed or refractory disease >12 months after completion of first-line therapy if no intention to proceed to transplant; OR
  • Used as additional therapy for relapsed or refractory disease >12 months after completion of first-line therapy and a partial response following second-line therapy (Note: For DLBCL, FL grade 3b, or PMBCL, patient must also have no intention to proceed to transplant); OR
  • Used for relapsed or refractory disease after two (2) or more lines of systemic therapy; OR

• Patient has Follicular Lymphoma Grade 1, 2, or 3a; AND
  • Patient has relapsed or refractory disease; AND
  • Patient has received at least two (2) prior lines of therapy; OR
• Patient has Richter’s transformation of CLL to DLBCL; AND
  • Patient received at least two (2) prior lines of chemoimmunotherapy for indolent or transformed disease which must have included an anthracycline or anthracenedione-based regimen, unless contraindicated; OR

• Patient has histologic transformation of an indolent lymphoma (follicular lymphoma or marginal zone lymphoma) to DLBCL; AND
  • Disease is refractory to first-line chemoimmunotherapy or has relapsed within 12 months of first-line chemoimmunotherapy; AND
    • Patient is a candidate for autologous hematopoietic stem cell transplant (HSCT); OR
  • Disease is relapsed or refractory after first-line chemoimmunotherapy and patient is NOT eligible for HSCT; OR
  • Patient received at least two (2) prior lines of chemoimmunotherapy for indolent or transformed disease which must have included an anthracycline or anthracenedione-based regimen, unless contraindicated

Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL) † ‡ Ф ^1,7,8,15

• Used for relapsed or refractory disease; AND
• Patient has received at least 2 prior lines of therapy including a Bruton tyrosine kinase (BTK) inhibitor (e.g., acalabrutinib, ibrutinib, pirtobrutinib, zanubrutinib, etc.) AND a B-cell lymphoma 2 (BCL-2) inhibitor (e.g., venetoclax, etc.)

Pediatric Aggressive Mature B-Cell Lymphomas ‡ ^1,7,12

• Patient is ≤ 18 years of age; AND
• Patient has primary mediastinal large B-Cell lymphoma; AND
• Used as consolidation or additional therapy in patients with a partial response after therapy for relapsed or refractory disease; AND
• Patient has previously received ≥ 2 prior chemoimmunotherapy regimens

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

4. Renewal Criteria ¹

Coverage cannot be renewed.

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• Q2054 – Lisocabtagene maraleucel, up to 110 million autologous anti-cd19 car-positive viable t cells, including leukapheresis and dose preparation procedures, per therapeutic dose

NDC:

• Breyanzi suspension for intravenous infusion [Each vial contains between 6.9 × 10⁶ and 322 x 10⁶ CAR-positive viable T cells in 4.6 mL cell suspension (between 1.5 × 10⁶ and 70 x 10⁶ CAR-positive viable T cells/mL)]: 73153-0900-xx

7. References

1. Breyanzi [package insert]. Bothell, WA; Juno Therap., Inc., May 2024. Accessed May 2024.
2. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. doi: 10.1016/S0140-6736(20)31366-0. Epub 2020 Sep 1.
3. Mejstrikova E, Hrusak O, Borowitz MJ, et al. CD19-negative relapse of pediatric B-cell precursor acute lymphoblastic leukemia following blinatumomab treatment. Blood Cancer J. 20177; 659. DOI 10.1038/s41408-017-0023-x
4. Ruella M, Maus MV. Catch me if you can: Leukemia Escape after CD19-Directed T Cell Immunotherapies. Computational and Structural Biotechnology Journal 14 (2016) 357–362.
5. Braig F, Brandt A, Goebeler M, et al. Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking. Blood; 129:1, 2017 Jan.
6. Majzner RG, Mackall CL. Tumor Antigen Escape from CAR T-cell Therapy. Cancer Discov 2018;8:1219-1226.
7. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) lisocabtagene maraleucel. 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 March 2024.
8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Version 3.2024. National Comprehensive Cancer Network, 2024. 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 Guidelines, go online to NCCN.org. Accessed March 2024.
9. Kamdar M, Solomon SR, Arnason J, et al.; TRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022 Jun 18;399(10343):2294-2308. doi: 10.1016/S0140-6736(22)00662-6.
10. Sehgal AR, Hildebrandt G, Ghosh N, et al. Lisocabtagene maraleucel (liso-cel) for treatment of second-line (2L) transplant noneligible (TNE) relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphoma (NHL): Updated results from the PILOT study. Journal of Clinical Oncology 2020 38:15_suppl, 8040-8040. DOI: 10.1200/JCO.2020.38.
11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas Version 5.2023. National Comprehensive Cancer Network, 2023. 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 Guidelines, go online to NCCN.org. Accessed October 2023.
12. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Aggressive Mature B-Cell Lymphomas Version 1.2023 National Comprehensive Cancer Network, 2023. 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 Guidelines, go online to NCCN.org. Accessed October 2023.
13. Abramson JS, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study. Blood 2023;141:1675-1684.
14. Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol 2022;23:1066-1077.
15. Siddiqi T, Maloney DG, Kenderian SS, et al. Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study. Lancet. 2023 Aug 19;402(10402):641-654. doi: 10.1016/S0140-6736(23)01052-8. Epub 2023 Jun 6. PMID: 37295445.

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/LCA/LCD):  N/A

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