In a phase II study reported in The Lancet Oncology, L. Elizabeth Budde, MD, PhD, and colleagues found that mosunetuzumab—a CD20 × CD3 T-cell–engaging bispecific antibody that redirects T cells to eliminate malignant B cells—produced a high rate of complete response in patients with relapsed or refractory follicular lymphoma.

Study Details

The study included 90 patients from sites in Australia, Canada, Germany, South Korea, Spain, the United Kingdom, and the United States who had received two or more prior lines of treatment, including an anti-CD20 therapy and an alkylating agent. Patients were enrolled between May 2019 and Sept 2020. Mosunetuzumab was given in 21-day cycles at 1 mg on cycle 1 day 1; 2 mg on cycle 1 day 8; 60 mg on cycle 1 day 15 and cycle 2 day 1; followed by 30 mg on day 1 of cycle 3 and day 1 of subsequent cycles. Patients with a complete response stopped treatment after cycle 8; those with partial response or stable disease continued treatment for up to 17 cycles.

L. Elizabeth Budde, MD, PhD

The primary endpoint was independent review committee–assessed complete response rate in all patients, with a comparison vs a 14% historical control complete response rate in a similar patient population receiving the PI3K inhibitor copanlisib.

Responses

At data cutoff (in August 2021), median follow-up was 18.3 months (interquartile range [IQR] = 13.8–23.3 months). Complete response was achieved in 54 patients (60.0%, 95% confidence interval [CI] = 49.1%–70.2%), a rate significantly higher than the historical rate with copanlisib (P < .0001).  Overall, objective response was achieved in 72 patients (80.0%). Median duration of response was 22.8 months (95% CI = 9.7 months–not reached) among all responders and 22.8 months (95% CI = 18.7 months–not reached) among complete responders; an estimated 56.9% of objective responses and 70.2% of complete responses persisted for ≥ 18 months.

The median number of cycles received was eight (IQR = 8-8). Median time to first response was 1.4 months; median time to complete response was 3.0 months. Among 16 patients who received more than eight cycles, a late initial response or deepening of initial response was observed in 6 (38%), including 5 (31%) who achieved complete response.

Median progression-free survival was 17.9 months (95% CI = 10.1 months–not reached), with 12- and 18-month rates of 57.7% and 47.0%.

Adverse Events

The most common adverse event of any grade was cytokine-release syndrome (44%; 26% grade 1 and 17% grade 2), which primarily was observed in cycle 1. The most common grade 3 or 4 adverse events were neutropenia/decreased neutrophil count (27%), hypophosphatemia (17%), hyperglycemia (8%), and anemia (8%).

Serious adverse events occurred in 47% of patients, most commonly infections (20%). Neurologic adverse events considered related to treatment consisted of confusion in three patients, disturbance in attention in one, and cognitive disorder in one (all grade 1 or 2). No treatment-related deaths were observed.

The investigators concluded, “Fixed-duration mosunetuzumab has a favorable safety profile and induces high rates of complete remissions, allowing potential administration as an outpatient regimen in patients with relapsed or refractory follicular lymphoma and two or more previous therapies.”

Nancy L. Bartlett, MD, of Siteman Cancer Center, Washington University School of Medicine, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by F. Hoffmann-La Roche and Genentech. For full disclosures of the study authors, visit thelancet.com.