Mosunetuzumab shows deep, durable responses in advanced follicular lymphoma
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Mosunetuzumab more than quadrupled the complete response rate among patients with relapsed or refractory follicular lymphoma, according to results of a pivotal phase 2 study.
Seventy-six percent of patients in the study who had a complete response were free of disease-related complications and did not require further treatment 1 year after receiving mosunetuzumab (Genentech).
Follicular lymphoma is a disease with a high rate of relapse for which each subsequent line of therapy is known to be less effective, L. Elizabeth Budde, MD, PhD, oncologist and associate professor at City of Hope Comprehensive Cancer Center, said during a presentation at ASH Annual Meeting and Exposition.
“Mosunetuzumab will help patients obtain chemotherapy-free treatment for follicular lymphoma, which can lead to a better quality of life,” she told Healio. “This treatment offers very durable and efficacious results.”
Budde said mosunetuzumab would be safe and effective option for patients who cannot tolerate more intense therapy or who are at high risk for complications.
"It's a readily available, off-the-shelf immunotherapy, and because of its favorable safety profile, there is a very good chance that mosunetuzumab can be administered in the community setting,” she added.
Budde and colleagues presented results of the pivotal phase 2 dose-expansion study of mosunetuzumab — an investigational CD20/CD3 bispecific T-cell-engaging antibody — for adults with relapsed or refractory follicular lymphoma who have received at least two previous lines of therapy.
The study enrolled 90 patients (median age, 60 years; range, 29-90; 61.1% male), 68.9% of whom were refractory to their prior line of therapy. Patients received a median of three (range, 2-10) previous lines of therapy and 78.9% were refractory to previous CD20-directed therapy.
Patients received IV mosunetuzumab in 21-day cycles with step-up dosing (1 mg/2 mg /60 mg /30 mg). Patients who achieved a complete response to therapy by cycle 8 discontinued study therapy, whereas those with a partial response or stable disease continued therapy until they completed 17 cycles or experienced disease progression or unacceptable treatment-related toxicity.
Improvement in the complete response rate was the study’s primary endpoint. Secondary endpoints included objective response rate, duration of response, PFS, safety and tolerability.
Median follow up was 18.3 months (range, 2–22.1) as of the data cutoff date of Aug. 27, 2021.
The study met its primary endpoint with a 60% (95% CI, 49-70; n = 54) complete response rate, which was significantly higher than the 14% historical control rate. The ORR was 80% (95% CI, 70-88; n = 72) for patients who received mosunetuzumab.
Median duration of response was 22.8 months (95% CI, 9.7 to not estimable) among those who responded to therapy. Median PFS was 17.9 months (95% CI, 10.1 to not estimable).
The 1-year EFS rate was 62% among patients who responded to treatment with mosunetuzumab and 76% for those who had a complete response.
Ninety-two percent of patients had at least one treatment-related adverse event, with cytokine release syndrome occurring most frequently, in 44.4% of patients.
Most cases of CRS were grade 1 or grade 2 and occurred during the first cycle of treatment, Budde said.
Two patients had grade 3 or grade 4 CRS, and all cases of CRS in the study were resolved.
Two deaths occurred during the study — malignant neoplasm progression and unexplained death — neither of which was attributed to the study drug.
The results demonstrated that mosunetuzumab has an extremely favorable safety profile for an immunotherapy Budde said, adding that the study protocol did not require mandatory hospitalization after infusions.
The neurologic toxicity rate was 4.4%, with no grade 3 or higher events. Additionally, only four of 90 patients in the study discontinued treatment because of adverse events.
“Mosunetuzumab is a very manageable, very efficacious therapy,” Budde told Healio. “I certainly hope this will be made commercially available to patients, especially in the community setting.”
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