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Loncastuximab tesirine-lpyl (Zynlonta®)
08.00.59c

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Loncastuximab tesirine (Zynlonta), administered by intravenous (IV) infusion,​ is considered medically necessary and, therefore, covered for the treatment of adult individuals with relapsed or refractory large B-cell lymphoma (including partial response, no response, or progressive disease but excluding bulky disease [tumor ≥10 cm in longest dimension] and active central nervous system lymphoma) after two or more lines of systemic therapy including any of the following types of lymphoma: 
  • Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS) 
  • High-grade B-cell lymphoma including NOS, translocations of MYC and BCL2 and/or BCL6 (double/triple hit lymphoma) 
  • Acquired immunodeficiency syndrome (AIDS)​​/human immunodeficiency virus (HIV)-related DLBCL, primary effusion lymphoma, human herpesvirus (HHV) 8–positive DLBCL
  • ​Posttransplant lymphoproliferative disorders 
Loncastuximab tesirine (Zynlonta), administered by IV infusion, is considered medically necessary and, therefore, covered for the treatment of adult individuals with histologic transformation of ​a low-grade or indolent lymphoma to DLBCL​*  in noncandidates for hematopoietic stem cell transplant (HSCT)​, who have been previously treated wtih an anthracycline-based regimen, for either of the following: 
  • As ​additional therapy for partial response, no response, or progressive disease following chemoimmunotherapy 
  • For individuals who have received multiple prior therapies for indolent or transformed disease
*Including follicular lymphoma (grade 1–2), extranodal marginal zone lymphoma (MZL) of the stomach (formerly called gastric mucosa-associated lymphoid tissue [MALT] lymphoma), extranodal MZL of nongastric sites (noncutaneous) (formerly called nongastric MALT lymphoma [noncutaneous]), splenic MZL, and nodal MZL. ​

EXPERIMENTAL/INVESTIGATIONAL

All other uses for loncastuximab tesirine (Zynlonta) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on Off-label Coverage for Prescription Drugs and Biologics.

MANDATES

PENNSYLVANIA MEMBERS
In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have Stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive agents" (08.01.08) for additional information regarding the applicable coverage of drugs and biologics.​

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, loncastuximab tesirine (Zynlonta) is covered under the medical benefits of the Company's products when the medical necessity criteria listed in this medical policy are met.
 
US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Loncastuximab tesirine-lpyl (Zynlonta) was approved by the FDA on April 23, 2021, for the treatment of individuals 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, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma.

This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

PEDIATRIC USE
The safety and effectiveness of loncastuximab tesirine (Zynlonta) in pediatric individuals have not been established.

Description

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). Individuals with DLBCL who are treated with first-line therapy can become refractory to therapy or relapse after initially responding to therapy. Individuals who become refractory to therapy, or relapse or progress after therapy, often have a poor prognosis.

Loncastuximab tesirine (Zynlonta) is an antibody-drug conjugate targeting cluster of differentiation (CD)19. The monoclonal immunoglobulin (Ig)G1 kappa antibody component binds to human CD19, a transmembrane protein expressed on the surface of cell of B-lineage origin. Upon binding to CD19, loncastuximab tesirine (Zynlonta) is internalized followed by release of SG3199 via proteolytic cleavage. The released SG3199 binds to the deoxyribonucleic acid (DNA) minor groove and forms highly cytotoxic DNA interstrand crosslinks, subsequently inducing cell death.

Loncastuximab tesirine (Zynlonta) was evaluated for efficacy in the LOTIS-2 trial (NCT03589469), ​which was an open-label, single-arm phase II trial involving 145 individuals age 18 or older with relapsed or refractory DLBCL who had received at least two prior systemic therapies. The primary endpoint for efficacy was overall response rate (ORR). Secondary endpoints were duration of response (DOR), complete response rate (CRR), relapse-free survival, progression-free survival (PFS), and overall survival (OS). The results were provided for the as-treated population of individuals. The ORR was 48.3 percent (95 percent confidence interval [CI], 39.9–56.7). Thirty-five of 145 individuals (24.1 percent) had complete responses and 35 of 145 individuals (24.1 percent) had partial responses. The median DOR was 10.3 months (95 percent CI, 6.9–not estimable). The median relapse-free survival was 13.4 months. The median PFS was 4.9 months (95 percent CI, 2.9–​8.3). The median OS was 9.9 months. The most common grade 3 or higher adverse events were neutropenia, thrombocytopenia, and increased gamma-glutamyl transferase (GGT).

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

​American Cancer Society. Types of B-cell lymphoma. 01/29/2019. Available at: https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/b-cell-lymphoma.html. Accessed August 31, 2023.

American Hospital Formulary Service (AHFS). Drug Information 2023. Loncastuximab tesirine-lpyl (Zynlonta®). [Lexicomp Online Web site]. 04/21/2023. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed August 31, 2023.

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(6):790-800.

ClinicalTrials.gov. Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (LOTIS-2). ClinicalTrials.gov Identifier: NCT03589469. First Posted: July 18, 2018. Last Update Posted: August 29, 2023. Available at: https://clinicaltrials.gov/. Accessed August 31, 2023.​

Elsevier's Clinical Pharmacology Compendium. Loncastuximab tesirine-lpyl (Zynlonta®). [Clinicalkey Web site]. 03/08/2023. Available at: https://www.clinicalkey.com/phamacology/ [via subscription only]. Accessed August 31, 2023.

Lexi-Drugs Compendium. Loncastuximab tesirine-lpyl (Zynlonta®). [Lexicomp Online Web site]. 06/27/2023. Available at: https://online.lexi.com/lso/action/home [via subscription only]. Accessed August 31, 2023.

Merative Micromedex® DRUGDEX® (electronic version). Loncastuximab tesirine-lpyl (Zynlonta®). [Micromedex Web site]. Merative L.P., Ann Arbor, Michigan, USA. 09/21/2023. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed August 31, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® – B-Cell Lymphomas V4.2023. [NCCN website]. 06/02/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf [via subscription only]​. Accessed August 31, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium®. [NCCN Web site]. Loncastuximab tesirine-lpyl (Zynlonta®). 2023. Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed August 31, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Labeling for Loncastuximab tesirine-lpyl (Zynlonta®). [FDA Web site]. 10/12/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 31, 2023.​

Zynlonta® (loncastuximab tesirine-lpyl) [prescribing information]. Epalinges, Switzerland: ADC Therapeutics SA; 10/2022. Available at: https://www.zynlonta.com/. Accessed August 31, 2023.​

Coding

CPT Procedure Code Number(s)
N/A
ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)
N/A
HCPCS Level II Code Number(s)

J9359 Injection, loncastuximab testirine-lpyl, 0.075 mg​

Revenue Code Number(s)
N/A





Coding and Billing Requirements

Policy History

Revisions From 08.00.59c:
10/23/2023

This version of the policy will become effective 10/23/2023. 

The policy criteria have been revised in accordance with National Comprehensive Cancer Network (NCCN) compendium and guidelines for B-cell lymphomas (V4.2023; 06/02/2023).


The indication for post-transplant lymphoproliferative disorders was added in accordance with NCCN 


Revisions From 08.00.59b:​
12/19/2022

This version of the policy will become effective 12/19/2022. 
​
The following policy criteria have been added to this policy:
Additional indications for B-cell lymphomas in accordance with National Comprehensive Cancer Network (NCCN) compendium and guidelines (V5.2022; 07/15/2022).

The following ICD-10 codes have been removed ​from this policy:
C83.30, C83.31, C83.32, C83.33, C83.34, C83.35, C83.36, C83.37, C83.38, C83.39,
C83.90, C83.91, C83.92, C83.93, C83.94, C83.95, C83.96, C83.97, C83.98, C83.99,
C85.20, C85.21, C85.22, C85.23, C85.24, C85.25, C85.26, C85.27, C85.28, C85.29​

Revisions From​ 08.00.59a:
04/01/2022
This version of the policy will become effective 04/01/2022.

​Inclusion of a policy in a Code Update memo does not imply that a full review of

the policy was completed at this time.


The following HCPCS codes have been removed from this policy:
C9084: Injection, loncastuximab tesirine-lpyl, 0.1 mg

J3590: Unclassified biologics

The following HCPCS code has been added to this policy:

J9359: Injection, loncastuximab tesirine-lpyl, 0.075 mg​​​


Revisions From 08.00.59:
10/01/2021

The following new policy has been developed to communicate the Company’s coverage criteria for loncastuximab tesirine-lpyl (Zynlonta™). The policy will become effective ​10/01/2021.​

10/23/2023
10/23/2023
08.00.59
Medical Policy Bulletin
Commercial
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Independence Blue Cross is a subsidiary of Independence Health Group, Inc. — independent licensees of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.