On December 22, 2022, mosunetuzumab-axgb, a bispecific CD20-directed CD3 T-cell engager, was granted accelerated approval for adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.1
Supporting Efficacy Data
Approval was based on findings in the multicenter, multicohort GO29781 study (ClinicalTrials.gov identifier NCT02500407), with an efficacy population of 90 patients who had received at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent. Patients received up to eight 21-day cycles consisting of step-up doses 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 to cycle 8, only on day 1 of each cycle, 30 mg.After 8 cycles, patients with a complete response discontinued therapy, and those with a partial response or stable disease continued treatment with 30 mg on day 1 of each subsequent 21-day cycle, for up to 17 cycles.
Mosunetuzumab has a boxed warning for cytokine-release syndrome and warnings/precautions for neurologic toxicity, infections, cytopenias, tumor flare, and embryofetal toxicity.
An objective response on independent review was observed in 72 patients (80%, 95% confidence interval [CI] = 70%–88%), with a complete response in 54 (60%). With a median follow-up of 14.9 months among responders, the estimated median duration of response was 22.8 months (95% CI = 10 months to not reached), with 62% and 57% of responses ongoing at 12 and 18 months, respectively.
How It Is Used
The recommended dose of mosunetuzumab is: 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 to cycle 8, only on day 1 of each cycle, 30 mg.Treatment should be given for eight cycles unless disease progression or unacceptable toxicity occurs. After eight cycles, patients with a complete response should discontinue therapy. Those with a partial response or stable disease should continue treatment with 30 mg on day 1 of each subsequent 21-day cycle for up to 17 cycles in the absence of disease progression or unacceptable toxicity.
Product labeling provides instructions on premedication and on dosage modifications for adverse reactions, including cytokine-release syndrome and immune effector cell–associated neurotoxicity and other neurologic toxicity.
Among the 90 patients in GO29781, the most common adverse events of any grade were cytokine-release syndrome (44%), fatigue (42%), rash (39%), and headache (32%). The most common grade 3 or 4 adverse events included rash (4.4%) and cytokine-release syndrome (2.2%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (98%), decreased phosphate (48%), increased glucose (42%), and decreased neutrophils (40%). Serious adverse events occurred in 47% of patients, most commonly (≥ 2%) cytokine-release syndrome, infection, renal insufficiency, pyrexia, and tumor flare. Adverse events led to discontinuation of treatment in 3%.
Mosunetuzumab has a boxed warning for cytokine-release syndrome and warnings/precautions for neurologic toxicity, infections, cytopenias, tumor flare, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving mosunetuzumab.
1. Lunsumio (mosunetuzumab-axgb) injection, for intravenous use, prescribing information, Genentech, Inc., December 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf. Accessed January 10, 2023.