Loncastuximab Tesirine-lpyl (Zynlonta)
Number: 0994
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses loncastuximab tesirine-lpyl (Zynlonta) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.
Note: Requires Precertification:
Precertification of loncastuximab tesirine-lpyl (Zynlonta) is required of all Aetna participating providers and members in applicable plan designs. For precertification of loncastuximab tesirine-lpyl (Zynlonta), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.
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Criteria for Initial Approval
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Large B-cell Lymphoma
Aetna considers loncastuximab tesirine-lpyl (Zynlonta) medically necessary for treatment of large B-cell lymphoma (e.g., DLBCL NOS, DLBCL arising from low grade lymphoma, high-grade B-cell lymphoma) when the member has partial response, no response, relapsed, progressive or refractory disease and all of the following criteria are met:
- The member has received two or more prior lines of systemic therapy; and
- The requested medication will be used as a single agent.
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Histologic Transformation of Indolent Lymphomas to Diffuse Large B-cell Lymphoma
Aetna considers loncastuximab tesirine-lpyl (Zynlonta) medically necessary for treatment of histologic transformation of indolent lymphomas to diffuse large B-cell lymphoma when the member has partial response, no response, progressive or relapsed disease and all of the following criteria are met:
- The member has received treatment with an anthracycline-based regimen (e.g., doxorubicin); and
- The member is not a candidate for transplant.
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HIV-Related B-cell Lymphomas
Aetna considers loncastuximab tesirine-lpyl (Zynlonta) medically necessary for treatment of HIV-related diffuse large B-cell lymphoma, primary effusion lymphoma, and human herpesvirus-8 (HHV8)-positive diffuse large B-cell lymphoma when the member has partial response, relapsed, progressive or refractory disease and all of the following criteria are met:
- The member has received two or more lines of systemic therapy; and
- The requested medication will be used as a single agent.
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Post-Transplant Lymphoproliferative Disorders (PTLD)
Aetna considers loncastuximab tesirine-lpyl (Zynlonta) medically necessary for treatment of monomorphic PTLD (B-cell type) when the member has partial response, relapsed, progressive or refractory disease and all of the following criteria are met:
- The member has received two or more lines of systemic therapy; and
- The requested medication will be used as a single agent.
Aetna considers all other indications as experimental, investigational, or unproven.
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Continuation of Therapy
Aetna considers continuation of loncastuximab tesirine-lpyl (Zynlonta) therapy medically necessary for members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.
Dosage and Administration
Loncastuximab tesirine-lpyl (Zynlonta) is available for injection as 10 mg of loncastuximab tesirine-lpyl as a lyophilized powder in a single-dose vial for reconstitution and further dilution for intravenous infusion.
Diffuse Large B-cell Lymphoma
Zynlonta is administered as an intravenous infusion over 30 minutes on day 1 of each cycle (every 3 weeks). The recommended dosage is as follows:
- 0.15 mg/kg every 3 weeks for 2 cycles;
- 0.075 mg/kg every 3 weeks for subsequent cycles.
Premedication with dexamethasone 4 mg orally or intravenously is given twice daily for 3 days beginning the day before Zynlonta administration.
Source: ADC Therapeutics, 2022
Background
U.S. Food and Drug Administration (FDA)-Approved Indications
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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 (NOS), DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma.
Compendial Uses
- Histologic transformation of indolent lymphomas to diffuse large B-cell lymphoma
- Human immunodeficiency virus (HIV)-related B-cell lymphomas
- Post-transplant lymphoproliferative disorders
Loncastuximab tesirine-lpyl is available as Zynlonta (ADC Therapeutics America) is an antibody and alkylating agent conjugate targeting CD19. Loncastuximab tesirine-lpyl binding to CD19 results in the release of SG3199 via proteolytic cleavage. Subsequently, SG3199 binds to the DNA minor groove and produces highly cytotoxic DNA interstrand crosslinks and ensuing cell death (ADC Therapeutics, 2021b).
Loncastuximab tesirine-lpyl (Zynlonta) carries the following warnings and precautions:
- Effusion and edema
- Myelosuppression
- Cutaneous reactions
- Embryo-fetal toxicity.
Per the prescribing information, the most common (≥ 20%) adverse reactions include thrombocytopenia, increased gamma-glutamyl transferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.
Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most frequent histologic subtype of non-Hodgkin lymphoma (NHL) responsible for an estimated 25 % of NHL cases worldwide. DLBCL is a heterogenous group of cancer cells consisting of large, transformed B cells with distinct nucleoli and basophilic cytoplasm, a diffuse growth pattern and a high proliferation fraction. Cancer cells in DLBCL generally express pan B cell antigens (CD19, CD20, CD22, CD79a) (Freedman and Aster, 2023). Refractory and relapsed DLBCL are characterized by disease recurrence after achieving a complete remission or disease that fails to respond adequately to treatment, respectively (UpToDate, 2021). Patients who fail first-line therapy have poor prognoses and disease worsening with each line of therapy. The chance for cure or long-term disease-free survival (DFS) decreases in this patient population (ADC Therapeutics, 2021).
On April 23, 2021, the U.S. Food and Drug Administration (FDA) approved Zynlonta (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and high-grade B-cell lymphoma. The FDA granted accelerated approval based on supporting data from the LOTIS-2 study (ADC Therapeutics, 2021).
The LOTIS-2 study consisted of a large phase-II, multi-national, open-label, single-arm clinical trial of 145 adult patients with relapsed or refractory DLBCL following at least 2 prior systemic regimens. Zynlonta was administered as 0.15 mg/kg every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks for subsequent cycles until disease progression or unacceptable toxicity. Efficacy evaluation was based on overall response rate (ORR). The trial demonstrated an ORR in 48.3 % (70/145) of patients inclusive of a complete response (CR) in 24.1 % (35/145) of patients and a partial response (PR) in 24.1 % (35/145) of patients. A median time to response was noted as 1.3 months with a median duration of response (mDOR) for the 70 responders as 10.3 months.
References
The above policy is based on the following references:
- ADC Therapeutics America. ADC Therapeutics announces FDA approval of Zynlonta (loncastuximab tesirine-lpyl) in relapsed or refractory diffuse large B-cell lymphoma. Press Release. Murray Hill, NJ: ADC Therapeutics; April 23, 2021.
- ADC Therapeutics America. Zynlonta (loncastuximab tesirine-lpyl) for injection, for intravenous use. Prescribing Information. Murray Hill, NJ: ADC Therapeutics; revised October 2022.
- Calabretta E, Hamadani M, Carlo-Stella C, et al. The antibody-drug conjugate loncastuximab tesirine for the treatment of diffuse large B-cell lymphoma. Blood. 2022;140(4):303-308.
- Freedman AS, Aster JC. Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed June 2023.
- Freedman AS, Friedberg JW. Relapsed or refractory diffuse large B cell lymphoma. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed April 2021.
- Hamadani M, Chen L, Song Y, et al. Matching-adjusted indirect comparison of the efficacy of loncastuximab tesirine versus treatment in the chemoimmunotherapy era for relapsed/refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2022;22(8):e738-e744.
- Kim J, Cho J, Yoon SE, et al. Efficacy of salvage treatments in relapsed or refractory diffuse large B-cell lymphoma including chimeric antigen receptor T-cell therapy: A systematic review and meta-analysis. Cancer Res Treat. 2023 Mar 13 [Online ahead of print].
- National Comprehensive Cancer Network (NCCN). Loncastuximab tesirine-lpyl. NCCN Drugs and Biologics Compendium. Plymouth Meeting, PA: NCCN; April 2024.