About 80% of patients with relapsed or refractory (R/R) follicular lymphoma (FL) responded to treatment with mosunetuzumab, an immunoglobulin G1 (IgG1)-based bispecific antibody directed against CD20 and CD3, according to results of a phase II study published in Lancet Oncology.1
Nancy L. Bartlett, MD, of Washington University in St. Louis, and colleagues conducted a single-arm, phase II study at 49 centers in seven countries. The 90 subjects included patients with R/R FL and previous treatment with an anti-CD20 therapy and an alkylating agent.
Patients received intravenous mosunetuzumab in 21-day cycles with cycle one step-up dosing. Patients with complete response (CR) completed treatment after cycle eight; patients with partial response or stable disease continued treatment for up to 17 cycles.
“In contrast to therapies which continue until progression or intolerance, fixed-duration therapy has the potential to decrease the cost of a therapy and is preferred by patients since this potentially results in many fewer office visits and is less disruptive to their lives,” Dr. Bartlett explained.
With a median follow-up of 18.3 months, 60.0% of patients achieved CR. The CR rate was significantly higher than the observed historical control CR rate of 14% with copanlisib (p<0.0001).
Median time to response was short at 1.4 months, with a median of 3.0 months to reach CR. Median duration of response was 22.8 months, and median progression-free survival was 17.9 months. Response was maintained for 18 months or longer in 70.2% of complete responders and in 56.9% of all responders.
“The most exciting aspect of this treatment approach is the lack of short- and long-term bone marrow suppression,” Dr. Bartlett said.
The most common grade 3-4 adverse events (AEs) were neutropenia or decreased neutrophil count (27%), hypophosphatemia (17%), hyperglycemia (8%), and anemia (8%). Serious AEs occurred in about half of patients (47%), but there were no treatment-related grade 5 AEs. Cytokine release syndrome was mostly low-grade.
The researchers acknowledged that “both CAR [chimeric antigen receptor] T-cell therapies and bispecific antibodies are likely to have essential roles in the future management of [R/R FL]. However, mosunetuzumab is an off-the-shelf immunotherapy that avoids many of the logistical challenges associated with current CAR T-cell therapies.”
“This is an important addition to the treatment options for patients with multiply recurrent [FL],” Dr. Bartlett said. “It is a well-tolerated outpatient therapy with high overall and complete response rates. Early follow-up is encouraging in regard to durability of the complete remissions, but whether this treatment has the potential to ‘cure’ a subset of patients is unknown.”
In an accompanying editorial, Christian Buske, MD, of University Hospital Ulm in Germany, said these results indicated that “patients with [R/R FL] now have a new powerful treatment option available, which is off-the-shelf, easy to administer, and, with its toxicity profile, feasible for outpatient use.”2
Dr. Buske also cited data presented at the 2021 American Society of Hematology Annual Meeting that showed mosunetuzumab was successfully combined with lenalidomide in this patient population with no new AEs.
“This finding has already opened the way to a new phase III trial that will challenge rituximab plus lenalidomide in [R/R FL] by combining mosunetuzumab with lenalidomide and will possibly lead to trials testing superiority of this combination over immunochemotherapy in the first-line setting of [FL],” Dr. Buske said.
Any conflicts of interest declared by the authors can be found in the original articles.
References
- 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 [published online ahead of print, 2022 July 5]. Lancet Oncol. doi: 10.1016/S1470-2045(22)00335-7.
- Buske C. Mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma [published online ahead of print, 2022 July 5]. Lancet Oncol. doi: 10.1016/S1470-2045(22)00385-0.