Treatment with the investigational agent mosunetuzumab (RG7828) as monotherapy induced deep remissions in patients with relapsed/refractory follicular lymphoma, according to results of a recent trial presented at the ASH 2021 Annual Meeting and Exposition.
In this single-arm study of 90 pretreated patients, the objective response rate (ORR) was 78.9% (95% confidence interval [CI], 69%-87%), with a complete response (CR) rate of 57.8% (95% CI, 49%-70%), reported L. Elizabeth Budde, MD, PhD, Associate Professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA. The responses were durable, with a median duration of response of 22.8 months (95% CI, 9.7-not evaluable) among those who responded.
“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment,” said Dr Budde. “We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization.”
Mosunetuzumab is a bispecific CD20xCD3 antibody that engages and redirects T-cells to eliminate CD20-positive malignant B-cells. Unlike CAR T-cells, it can be infused directly into the bloodstream without requiring the removal and modification of the patient’s immune cells.
“Mosunetuzumab, whether given intravenously or subcutaneously, is available off-the-shelf because it is already premade and ready whenever the patient is ready to use it,” she said.
More than two-thirds (68.9%) of patients enrolled in the study were refractory to previous therapy. Patients had received a median of 3 previous lines of therapy and 78.9% were refractory to previous CD20-directed therapy.
In this phase 1/2 trial, mosunetuzumab was administered intravenously in 21-day cycles with step-up dosing starting at 1 mg in cycle 1 in an effort to mitigate cytokine release syndrome (CRS). Patients who achieved a CR by cycle 8 discontinued therapy; those with a partial response or stable disease continued treatment for a total of 17 cycles until disease progression or unacceptable toxicity.
As of data cutoff (August 27, 2021), the median follow-up was 18.3 months. The 58.7% CR rate met the primary end point and was significantly higher than the 14% historical CR rate (P <.0001), noted Dr Budde. The median time to first response was 1.4 months, and the median time to first CR was 3.0 months.
The primary end point of the study was CR by independent review. Response rates were similar across high-risk subgroups, including those with disease progression within 24 months of primary therapy (CR, 55%; ORR, 83%) and patients with double-refractory disease (CR, 48%; ORR, 69%).
The event-free survival rate at 1 year among responders was 65.4%, which improved to 80.1% among those who had a CR. The event-free survival rate at 18 months was 57%.
The median progression-free survival was 17.9 months (95% CI, 12.0-not evaluable).
Mosunetuzumab was well-tolerated, with 4.4% of patients discontinuing treatment due to adverse events (AEs). Grade 3/4 treatment-related AEs occurred in 51.1% of patients, and serious treatment-related AEs occurred in 33.3%.
CRS occurred in 44.4% of patients, with the majority of cases being grade 1 (25.6%) or grade 2 (16.7%). There were no cases of grade 5 CRS, and all cases resolved. The median time to CRS onset was 5.2 hours in cycle 1 and 26.6 hours in subsequent cycles. Management of CRS consisted of corticosteroids in 9 patients and tocilizumab (Actemra) in 7.
Immune effector cell–associated neurotoxicity syndrome occurred in 4.4% of patients. All cases were grade 1/2.
The availability of CAR T-cell therapies and mosunetuzumab for patients with follicular lymphoma is a “win-win” for patients, said Dr Budde. “Some patients may not have time to wait for CAR T-cell production and, therefore, a mosunetuzumab treatment off-the-shelf, readily available, will be appealing if there are any larger issues.”