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The European Commission has granted a conditional marketing authorization for mosunetuzumab for the treatment of adult patients with relapsed or refractory follicular lymphoma who have previously received at least 2 systemic therapies.
The European Commission has granted a conditional marketing authorization for mosunetuzumab (Lunsumio) for the treatment of adult patients with relapsed or refractory follicular lymphoma who have previously received at least 2 systemic therapies.1
The regulatory decision is supported by findings from the phase 1/2 GO29781 trial (NCT02500407), in which at a median follow-up of 18.3 months, the bispecific antibody elicited a complete response (CR) rate of 60% (95% CI, 49%-70%) per independent review facility (IRF) assessment in this patient population (n = 90).2 The objective response rate (ORR) achieved with the agent was 80% (95% CI, 70%-88%), and the median duration of response (DOR) was 22.8 months (95% CI, 9.7–not estimable [NE]).
“Having additional treatment options for people with follicular lymphoma, where multiple prior lines of therapy have failed, is critical to help them achieve better outcomes,” Elizabeth Budde, MD, PhD, hematologic oncologist and associate professor at City of Hope, stated in a press release. “It is exciting to have a new class of immunotherapy like [mosunetuzumab], offering a readily available, chemotherapy-free and fixed-duration treatment, with great potential to provide durable remissions without the need to stay on treatment continuously.”
Mosunetuzumab was designed to target CD20 on the surface of B cells and CD3 on the surface of T cells, and through this targeting approach it has been shown to redirect existing T cells to both engage and destroy target B cells by releasing cytotoxic proteins into them.
The multicenter, open-label, dose-escalation and -expansion trial enrolled patients with follicular lymphoma who had grade 1 to 3a disease, an ECOG performance status of 0 to 1, and who previously received 2 or more systemic regimens, including at least 1 anti-CD20 antibody and at least 1 alkylating agent.
Participants (n = 90) received mosunetuzumab every 3 weeks as part of 21-day cycles through a step-up dosing approach in cycle 1. In the first cycle, mosunetuzumab was given at 1 mg on day 1, at 2 mg on day 8, and at 60 mg on day 15. In cycle 2, the bispecific antibody was administered at 60 mg on day 1. Moreover, in the third cycle and beyond, the agent was given at 30 mg on day 1. If patients achieved a CR following cycle 8, they were given 17 cycles of treatment. The initial dose of the agent was given without mandatory hospitalization.
The primary end point was CR rate per IRF assessment, and this was evaluated in comparison with the historical CR rate of 14%. Secondary end points comprised ORR, DOR, and progression-free survival (PFS). Safety and tolerability were also examined.
Most of the patients included in the early-phase study had advanced disease and were considered to be heavily pretreated, with poor-prognosis characteristics. The median number of previous lines of treatment received was 3, with a range of 2 to 10. All patients had received an anti-CD20 therapy and an alkylating agent. Additionally, 18.9% of patients received a prior PI3K inhibitor, 14.4% had a prior immunomodulatory drug, and 3.3% had prior CAR T-cell therapy.
Notably, 68.9% of patients were refractory to the last therapy they had received, with 78.9% refractory to prior anti-CD20 therapy and 53.3% refractory to both an anti-CD20 therapy and an alkylating agent.
Additional findings presented during the 2021 ASH Annual Meeting indicated that mosunetuzumab elicited an investigator-assessed CR rate of 60% (95% CI, 49%-70%), and an investigator-assessed ORR of 78% (95% CI, 68%-86%). The CR rates produced with the agent in high-risk subgroups were noted to be similar to that of the overall study population.
In those who were younger than 65 years of age (n = 60), the CR rate with the bispecific antibody was 55% (95% CI, 42%-68%) vs 70% (95% CI, 51%-85%) in those aged 65 years or older (n = 30). Moreover, the CR rate with the agent was 74% (95% CI, 56%-87%) in those who previously received 2 lines of therapy (n = 34) vs 52% (95% CI, 39%-65%) in those who received 3 or more prior lines of treatment (n = 56).
Additionally, the CR rates were 52% (95% CI, 39%-65%) and 79% (95% CI, 59%-92%), respectively, in those who were relapsed or refractory to their last prior therapy (n = 62) and in those who were not (n = 28). In the subset of patients who were double refractory (n = 48), mosunetuzumab produced a CR rate of 50% (95% CI, 35%-65%) vs 71% (95% CI, 55%-84%) in those who were not. Lastly, the CR rate was 57% (95% CI, 42%-72%) in those with POD24 disease (n = 47) vs 63% (95% CI, 47%-77%) in those who did not have this disease (n = 43).
The median time to response was 1.4 months (range, 1.1-8.9), and the median time to first CR was 3.0 months (range, 1.1-18.9). The median PFS with mosunetuzumab was 17.9 months (95% CI, 10.1-NE).
Regarding safety, the most common toxicity was cytokine release syndrome (CRS), which was observed in 39% and was noted to be low grade and to resolve by treatment completion; 14% of patients experienced grade 2 CRS. Other adverse effects that were frequently observed with mosunetuzumab included neutropenia, hypophosphatemia, pyrexia, and headache.