Medicare Advantage

Medical Policy

Title:

Mosunetuzumab-axgb (Lunsumio™)

Policy #:

MA08.158c

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.

In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.

MEDICALLY NECESSARY

INITIAL THERAPY

Mosunetuzumab-axgb (Lunsumio) is considered medically necessary and, therefore, covered for adult individuals for any of the following conditions for a maximum of eight cycles, when all of the following criteria are met:

Diffuse Large B-Cell Lymphoma

Second-line and subsequent therapy in combination with polatuzumab vedotin-piiq (Polivy) as National Comprehensive Cancer Network (NCCN)-preferred regimen, for one of the following:

relapsed disease <12 months after completion of first-line therapy or primary refractory disease in noncandidates for chimeric antigen receptor (CAR) T-cell therapy (includes individuals who do not have access to CAR T-cell therapy)
relapsed disease >12 months after completion of first-line therapy if no intention to proceed to transplant

Follicular Lymphoma, Classic

Relapsed or refractory follicular lymphoma (grade 1-3a) after two or more lines of systemic therapy*
Third-line and subsequent therapy (if not previously given) for partial response, no response, relapsed, or progressive disease in individuals with indications for treatment**, as NCCN-preferred regimen.

*Prior systemic therapy includes an anti-CD20 monoclonal antibody (e.g., rituximab, obinutuzumab) and an alkylating agent (e.g., bendamustine, cyclophosphamide).

** Indications for treatment: symptoms attributable to Follicular Lymphoma (not limited to B symptoms; defined as fever, drenching night sweats, and loss of more than 10 percent body weight over 6 months), threatened end-organ function, clinically significant or progressive cytopenia secondary to lymphoma, clinically significant bulky disease (any nodal or extranodal tumor mass with a diameter of ≥7 cm) and steady or rapid progression.

High-Grade B-Cell Lymphomas

Second-line and subsequent therapy in combination with polatuzumab vedotin-piiq (Polivy) for one of the following:

relapsed disease <12 months after completion of first-line therapy or primary refractory disease in non-candidates for CAR T-cell therapy (includes individuals who do not have access to CAR T-cell therapy)
relapsed disease >12 months after completion of first-line therapy if no intention to proceed to transplant
as alternative systemic therapy (if not previously used) for relapsed or refractory disease

Human Immunodeficiency Virus (HIV)-Related B-Cell Lymphomas

In combination with polatuzumab vedotin-piiq (Polivy) as second-line and subsequent therapy when all of the following criteria are met:

one of the following subtypes:

HIV-related diffuse large B-cell lymphoma
primary effusion lymphoma
HHV8-positive diffuse large B-cell lymphoma, not otherwise specified
HIV-related plasmablastic lymphoma

one of the following disease states:

relapsed disease <12 months after completion of first-line therapy or primary refractory disease in noncandidates for CAR T-cell therapy (includes individuals who do not have access to CAR T-cell therapy)
relapsed disease >12 months after completion of first-line therapy if no intention to proceed to transplant
as alternative systemic therapy (if not previously used) for relapsed or refractory disease

Post-Transplant Lymphoproliferative Disorders

Second-line and subsequent therapy in combination with polatuzumab vedotin-piiq (Polivy) for monomorphic PTLD (B-cell type) for one of the following:

relapsed disease <12 months after completion of initial treatment with chemoimmunotherapy or primary refractory disease in non-candidates for CAR T-cell therapy (includes individuals who do not have access to CAR T-cell therapy)
relapsed disease >12 months after completion of initial treatment with chemoimmunotherapy if no intention to proceed to transplant
as alternative systemic therapy (if not previously used) for relapsed or refractory disease

CONTINUATION THERAPY (BEYOND INITIAL EIGHT CYCLES)

Mosunetuzumab-axgb (Lunsumio) is considered medically necessary and, therefore, covered for continuation therapy of up to nine additional cycles (17 total cycles of treatment) for adult individuals who achieve partial response or have stable disease in response to eight cycles of treatment with mosunetuzumab-axgb (Lunsumio). (For individuals who achieve a complete response, no further treatment beyond eight cycles is required.)

EXPERIMENTAL/INVESTIGATIONAL

All other uses for mosunetuzumab-axgb (Lunsumio) 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.

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 service.

Guidelines

There is no Medicare coverage determination addressing mosunetuzumab-axgb (Lunsumio); therefore, the Company policy is applicable.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, mosunetuzumab-axgb (Lunsumio) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when mosunetuzumab-axgb (Lunsumio) is covered under a member's medical benefit (Part B benefit). It does not address instances when mosunetuzumab-axgb (Lunsumio) is covered under a member's pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Mosunetuzumab-axgb (Lunsumio) was approved by the US Food and Drug Administration (FDA) on December 22, 2022, for the treatment of adult individuals with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. Following an initial step-up dosing schedule, mosunetuzumab-axgb (Lunsumio) is administered once every 21 days for eight cycles, unless they experience unacceptable toxicity or disease progression. For individuals who achieve a complete response, no further treatment beyond eight cycles is required. For individuals who achieve a partial response or have stable disease in response to treatment after eight cycles, an additional nine cycles of treatment (17 cycles total) should be administered, unless they experience unacceptable toxicity or disease progression.

PEDIATRIC USE
The safety and effectiveness in pediatric individuals have not been established.

Description

FOLLICULAR LYMPHOMA

According to the American Cancer Society, about one of five lymphomas in the United States is a follicular lymphoma (FL). They are usually a slow-growing (indolent) lymphoma that occurs in adults aged 60 years and older.

MOSUNETUZUMAB-AXGB (LUNSUMIO)

Mosunetuzumab-axgb (Lunsumio) is a bispecific T-cell engager (BiTE) monoclonal antibody that creates a bridge between the T cell and the lymphoma cell, by binding to two different proteins at the same time (CD20 located on lymphoma cells and CD3 located on cytotoxic T cells). This binding triggers the release of proinflammatory cytokines and proliferation of T cells, which ultimately causes the death of the lymphoma cells.

CYTOKINE RELEASE SYNDROME
Cytokines are proteins that communicate with cells about the need for immune assistance. Cytokines are secreted by both healthy and cancerous cells. When mosunetuzumab-axgb (Lunsumio) infusion is initiated, a transient release (increase) of cytokines occurs in response to the T-cell activation, called cytokine release syndrome (CRS). The highest risk of CRS occurs during the first cycle of mosunetuzumab-axgb (Lunsumio), and typically subsides with subsequent doses. The risk is reduced by using step-up dosing schedule and pretreatment medications. Symptoms may include serious or life-threatening reactions, including hypotension, fever, hypoxia, chills, tachycardia, and headache.

PEER-REVIEWED LITERATURE
Summary

The efficacy of mosunetuzumab-axgb (Lunsumio) was evaluated in a Phase 2, open-label, single-arm, multicenter, multicohort study in 90 adults with relapsed or refractory grade 1–3a FL who had received at least two prior therapies, including an anti-CD20 monoclonal antibody and an alkylating agent. All participants had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and received a median of three prior therapies (range, 2–10). Mosunetuzumab-axgb (Lunsumio) was administered intravenously as an initial step-up dosing schedule for a median of eight cycles unless individuals experienced progressive disease or unacceptable toxicity. After eight cycles, individuals with a complete response (CR) discontinued therapy; individuals with a partial response (PR) or stable disease continued treatment up to 17 cycles, unless individuals experienced progressive disease or unacceptable toxicity.

The primary efficacy endpoints, assessed by an independent review facility, were objective response rate (ORR) (defined as CR or PR) and duration of response (DOR) (defined as the time from the initial occurrence of CR or PR to the first progressive disease or death due to any cause). The ORR was 80% (CR, 60%; PR, 20%). The median DOR was 22.8 months.

The most common adverse events were cytokine release syndrome (predominantly grade 1 or 2 and confined to the first cycle) (44%), fatigue (37%), and headache (31%). Grade 3 to 4 adverse events were reported in 51% of individuals (neutropenia or decreased neutrophil count, hypophosphatemia, hyperglycemia, and anemia). Serious adverse events were reported in 47% of individuals.

OFF-LABEL INDICATION

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. 02/15/2024. Available at: https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/b-cell-lymphoma.html. Accessed March 25, 2025.

American Hospital Formulary Service (AHFS). Drug Information 2025. Tisotumab vedotin-tftv (Tivdak). [Lexicomp Online Web site]. 04/10/2024. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 25, 2025.

Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055-1065.

Elsevier's Clinical Pharmacology Compendium. Mosunetuzumab-axgb (Lunsumio). 12/27/2024. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed March 25, 2025.

Lexi-Drugs Compendium. Mosunetuzumab-axgb (Lunsumio). 02/14/2025. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 25, 2025.

Lunsumio. [prescribing information]. South San Francisco, CA: Genentech, Inc.; original 11/2024. Available at: Genentech: Lunsumio™ (mosunetuzumab-axgb) - Information for Healthcare Providers. Accessed March 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Mosunetuzumab-axgb (Lunsumio). [NCCN Web site]. 2025. Available at: NCCN Drugs and Biologics Compendium® [via subscription only]. Accessed March 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - B-Cell Lymphomas V.2.2025. 02/10/2025. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf [via free subscription]. Accessed March 25, 2025.

PA House Bill – HB 427; Act 6. Signed February 12, 2020. Available at: https://www.legis.state.pa.us/cfdocs/billinfo/billinfo.cfm?syear=2019&sind=0&body=H&type=B&bn=0427. Accessed March 25, 2025.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Mosunetuzumab-axgb (Lunsumio). 02/27/2025. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 25, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Mosunetuzumab-axgb (Lunsumio) prescribing information and approval letter [FDA Web site]. 11/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed March 25, 2025.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)

J9350 Injection, mosunetuzumab-axgb, 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.158c:

06/16/2025

This version of the policy will become effective 06/16/2025.

This policy has been updated to communicate the Company's coverage position for mosunetuzumab-axgb (Lunsumio), in accordance with the National Comprehensive Cancer Network (NCCN).

Criteria for Classic Follicular Lymphoma has been revised.

The following indications have been added:

Diffuse Large B-Cell Lymphoma
High-Grade B-Cell Lymphomas
HIV-Related B-Cell Lymphomas
Post-Transplant Lymphoproliferative Disorders.

All of the ICD-10 CM codes have been removed from this policy, since they are informational. Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

Revisions From MA08.158b:

04/08/2024

This version of the policy will become effective 04/08/2024.

This policy has been updated to communicate the Company's coverage position for mosunetuzumab-axgb (Lunsumio), in accordance with National Comprehensive Cancer Network (NCCN), as a preferred regimen for partial response, no response, relapsed, or progressive follicular lymphoma (grade 1-3a).

Revisions From MA08.158a:

01/01/2024	Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
07/01/2023	This version of the policy will become effective 07/01/2023. 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: C9399 Unclassified drugs or biologicals J3590 Unclassified biologics The following HCPCS code has been added to this policy J9350 Injection, mosunetuzumab-axgb, 1 mg

01/01/2024

Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.

07/01/2023

This version of the policy will become effective 07/01/2023.

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:
C9399 Unclassified drugs or biologicals
J3590 Unclassified biologics

The following HCPCS code has been added to this policy
J9350 Injection, mosunetuzumab-axgb, 1 mg

Revisions From MA08.158:

03/27/2023

This version of the policy will become effective 03/27/2023.

The following new policy has been developed to communicate the Company's coverage criteria for mosunetuzumab-axgb (Lunsumio^TM).

Version Effective Date:

6/16/2025

Version Issued Date: