Mosunetuzumab-axgb (Lunsumio and Lunsumio Velo)

Number: 1025

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses mosunetuzumab-axgb (Lunsumio and Lunsumio Velo) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of mosunetuzumab-axgb (Lunsumio and Lunsumio Velo) is required of all Aetna participating providers and members in applicable plan designs. For precertification of mosunetuzumab-axgb (Lunsumio and Lunsumio Velo), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

1. Criteria for Initial Approval

   Aetna considers mosunetuzumab-axgb (Lunsumio or Lunsumio Velo) medically necessary for treatment of the following indications:

   1. Follicular Lymphoma

      For treatment of follicular lymphoma when both of the following criteria are met:

      1. The disease had a partial response or no response to treatment or the disease is relapsed or progressive, and
      2. The member has tried at least 2 prior lines of systemic therapy.

   2. Diffuse Large B-cell Lymphoma, High-Grade B-cell Lymphoma, HIV-Related B-cell Lymphomas, Post-Transplant Lymphoproliferative Disorders (PTLD) (Lunsumio IV only)

      For subsequent treatment of diffuse large B-cell lymphoma, high-grade B-cell lymphoma, HIV-related diffuse large B-cell lymphoma, primary effusion lymphoma, human herpesvirus-8 (HHV8)-positive diffuse large B-cell lymphoma, HIV-related plasmablastic lymphoma, and monomorphic post-transplant lymphoproliferative disorders (B-cell type) when both of the following criteria are met:

      1. The disease is relapsed or refractory; and
      2. The requested medication will be used in combination with polatuzumab vedotin.

      Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continuation of mosunetuzumab-axgb (Lunsumio or Lunsumio Velo) therapy (up to 17 cycles total) medically necessary in members requesting reauthorization for an indication listed in the Criteria for Initial Approval section when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Mosunetuzumab-axgb (Lunsumio)

Mosunetuzumab-axgb is supplied as Lunsumio 1mg/mL solution in a single-dose vial and 30 mg/30 mL (1 mg/mL) solution in a single-dose vial injections for intravenous infusion only.

Follicular Lymphoma

The recommended dosage for Lunsumio is as follows:

• Cycle 1 Day 1: 1 mg
• Cycle 1 Day 8: 2 mg
• Cycle 1 Day 15: 60 mg
• Cycle 2 Day 1: 60 mg
• Cycle 3 and beyond Day 1: 30 mg.

The rate of administration for cycle 1 is over a minimum of 4 hours. The rate of administration for cycles 2 and cycles 3 and beyond is over 2 hours if infusions from cycle 1 were well-tolerated. Administer Lunsumio for 8 cycles, unless individuals experience unacceptable toxicity or disease progression. No further treatment beyond 8 cycles is required for individuals who achieve a complete response. In individuals who achieve a partial response or have stable disease in response to treatment with Lunsumio after 8 cycles, an additional 9 cycles of treatment (17 cycles total) should be administered, unless an individual experiences unacceptable toxicity or disease progression. 

Refer to full prescribing information for Lunsumio for preparation and administration instructions, step-up dosing schedule to reduce the risk of cytokine release syndrome (CRS), and dosage modifications for adverse reactions.

Source: Genentech, 2025a

Mosunetuzumab-axgb (Lunsumio Velo)

Mosunetuzumab-axgb is supplied as Lunsumio Velo 5 mg/0.5 mL and 45 mg/mL solution in a single-dose vial for subcutaneous injection.

• Administer Lunsumio Velo only as a subcutaneous injection.
• Premedicate to reduce risk of cytokine release syndrome (CRS).
• The recommended dosage for Lunsumio Velo for subcutaneous injection is the following:
  
  

  Table: Recommended Dose and Schedule of Lunsumio Velo Subcutaneous Injection (21-Day Treatment Cycles)

  Day of Treatment		Subcutaneous Dose of Lunsumio Velo
  Cycle 1	Day 1	5mg
  	Day 8	45mg
  	Day 15	45mg
  Cycles 2+	Day 1	45mg

  See full prescribing information for instructions on preparation and administration.

Source: Genentech, 2025b

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96401	Chemotherapy administration, subcutaneous or intramuscular; non-hormonal anti-neoplastic
96413 – 96417	Chemotherapy administration, intravenous infusion technique
HCPCS codes covered if selection criteria are met:
J9350	Injection, mosunetuzumab-axgb, 1 mg [Mosunetuzumab-axgb (Lunsumio) and (Lunsumio Velo)]
Other HCPCS codes related to the CPB:
J9309	Injection, polatuzumab vedotin-piiq, 1 mg
ICD-10 codes covered if selection criteria are met:
C82.00 – C82.99	Follicular lymphoma
C83.30-C83.3A	Diffuse large B-cell lymphoma [covered when used with polatuzumab vedotin]
C83.80 - C83.8A	Other non-follicular lymphoma [Primary effusion lymphoma]
D47.Z1	Post-transplant lymphoproliferative disorder (PTLD) [covered when used with polatuzumab vedotin]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Lunsumio and Lunsumio Velo are indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

Compendial Uses (Lunsumio IV only)

• Follicular lymphoma
• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Human immunodeficiency virus (HIV)-related B-cell lymphomas
• Post-transplant lymphoproliferative disorders (B-cell type)

Mosunetuzumab-axgb (Lunsumio)

Mosunetuzumab-axgb is available as Lunsumio and Lunsumio Velo (Genentech, Inc.) which is a bispecific CD20-directed CD3 T-cell engager. It is a humanized monoclonal anti-CD20xCD3 T-cell-dependent bispecific antibody of the immunoglobulin GI (IgG1) isotype. Recombinant DNA technology is utilized to produce mosunetuzumab-axgb in Chinese Hamster Ovary (CHO) cells. Mosunetuzumab-axgb binds to the CD3 receptor expressed on the surface of lymphoma cells and certain healthy B-lineage cells. Mosunetuzumab-axgb activated T-cells, in vitro, resulted in the release of proinflammatory cytokines, and induced lysis of B-cells (Genentech, 2025b; 2025c).

According to the prescribing information, Lunsumio and Lunsumio Velo carry a boxed warning for cytokine release syndrome (CRS), including serious or life-threatening reactions. Initiate treatment with the Lunsumio or Lunsumio Velo step-up dosing schedule to reduce the risk of CRS. Withhold Lunsumio or Lunsumio Velo until CRS resolves or permanently discontinue based on severity. 

Per the prescribing information, Lunsumio carries the following warnings and precautions:

• Neurologic toxicity can be serious and may include immune effector cell-associated neurotoxicity syndrome (ICANS). Monitor patients for signs and symptoms of neurologic toxicity during treatment; withhold or permanently discontinue based on severity.
• Infections can be serious or fatal. Monitor patients for signs and symptoms of infection, including opportunistic infections, and treat as needed.
• Hemophagocytic lymphohistiocytosis can be serious or fatal. For suspected cases, interrupt Lunsumio or Lunsumio Velo and evaluate and treat promptly.
• Cytopenias: Monitor complete blood cell counts during treatment.
• Tumor flare reactions can be serious. Monitor patients at risk for complications of tumor flare.
• Risk of medication errors with incorrect product use: Ensure that the correct formulation is being prescribed, dispensed, and administered.
• Embryo-fetal toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.

Per the prescribing information, Lunsumio and Lunsumio Velo carry the following adverse reactions:

• The most common adverse reactions (≥ 20%) include: injection site reactions, cytokine release syndrome, fatigue, rash, pyrexia, headache, COVID-19 infection, musculoskeletal pain, and diarrhea.
• The most common Grade 3 to 4 laboratory abnormalities (≥ 15%) include: decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

Refer to full prescribing information for Lunsumio and Lunsumio Velo for use in specific populations.

On December 22, 2022, the U.S. Food and Drug Administration (FDA) granted approval to mosunetuzumab-axgb (Lunsumio), for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.  The FDA approval for Lunsumio was based on supporting data from the GO29781 study (FDA, 2022).

The GO29781 study was an open-label, single-arm, multicenter, multi-cohort, phase 2 trial, in which Budde and colleagues (2022) evaluated the safety and efficacy of mosunetuzumab-axgb (Lunsumio) in patients with relapsed or refractory follicular lymphoma (FL) who had received at least two prior therapies, including an anti-CD20 monoclonal antibody and an alkylating agent. Patients with active infections, history of autoimmune disease, prior allogeneic transplant, or any history of CNS lymphoma or CNS disorders were excluded from the study. Intravenous Lunsumio infusion was administered in 21-day cycles as step-up doses of 1 mg on cycle 1 day 1 and 2 mg on cycle 1 day 8, followed by 60 mg on cycle 1 day 15, and 60 mg on cycle 2 day 1, then 30 mg every 3 weeks in subsequent cycles. Lunsumio was administered for 8 cycles unless patients experienced unacceptable toxicity or disease progression. Following the 8 cycles, patients with a complete response discontinued therapy, whereas patients with a partial response or stable disease continued treatment up to 17 cycles, unless patients experienced an unacceptable toxicity or disease progression. The primary efficacy endpoint measures were objective response rate (ORR) and duration of response (DOR) assessed by an independent review facility according to standard criteria for non-Hodgkin's lymphoma (Cheson, et al., 2007). The evaluable efficacy population consisted of 90 patients with relapsed or refractory FL. The ORR was 80% (95% confidence interval [CI]: 70, 88), with 60% achieving complete responses. The median follow-up was 14.9 months among responders with the estimated median duration of response (DOR) of 22.8 months (95% CI: 10, not reached) and the estimated DOR rate at 12 months and 18 months as 62% and 57%, respectively. Of the 218 patients with hematologic malignancies who received Lunsumio at the recommended dose, cytokine release syndrome (CRS) occurred in 39% of patients, neurologic toxicity in 39% of patients (including immune effector cell-associated neurotoxicity syndrome [ICANS] in 1%), serious infections in 17%, and tumor flare in 4%. With regard to CRS, grade 2 occurred in 15%, grade 3 in 2%, and grade 4 in 0.5% (FDA, 2022; Genentech, 2025b).

On December 21, 2025, the U.S. Food and Drug Administration (FDA) granted approval to mosunetuzumab-axgb (Lunsumio Velo), a bispecific CD20-directed CD3 T-cell engager, as a subcutaneous (SC) formulation, for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. The FDA approval was based on supporting data from the Phase I/II G029781 (NCT02500407) study (Genentech, 2025c).

In the Phase I/II G029781, an open-label, multicenter, multicohort study, investigators evaluated the efficacy of mosunetuzumab-axgb (Lunsumio Velo) for the treatment of patients with relapsed or refractory FL after at least two lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent. Patients with active infections, history of autoimmune disease, prior alogeneic transplant, or any history of central nervous system (CNS) lymphoma or CNS disorders were excluded from the study. The investigators administered Lunsumio Velo as subcutaneous injection as 5 mg on Cycle 1 Day 1 and 45 mg on Cycle 1 Day 8, followed by 45 mg on Cycle 1 Day 15, then 45 mg every 3 weeks in subsequent cycles (a treatment cycle = 21 days). Patients received Lunsumio Velo for 8 cycles until experiencing progressive disease or unacceptable toxicity. Following 8 cycles, patients with the following: a complete response discontinued thereapy; a partial response or stable disease continued treatment up to 17 cycles, until they experienced progressive disease or unacceptable toxicity. Of the 94 evaluable adult patients, the median number of prior lines of systemic therapy was 3 (range: 2 to 9), with patients receiving one of the following the following: 2 prior lines (47%), 3 prior lines (19%), and 4 or more prior lines (34%). The primary efficacy outcome measures inclued objective response rate (ORR) and duration of response (DOR) as determined by an independent review facility using 2007 International Workign Group criteria. The median follow-up for DOR was 16 months. The results demonstrated that the ORR and complete response rate in patient receiving Lunsumio Velo was 75% (95% confidence interval [CI]: 64-83%) and 59% (95% CI: 48-69%), respectively. The cytokine release syndrome rate was 30% and events were mostly low grade (Grade 1-2, 28%; Grade 3, 2.1%), occurred during Cycle 1, and all resolved after a median duration of two days (range: 1-15) (Genentech, 2025a; 2025c).

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References