Monotherapy with the investigational bispecific antibody mosunetuzumab induced deep remissions in a phase 1/2 clinical trial of patients with relapsed or refractory follicular lymphoma.1
This single-arm study of 90 pretreated patients, the objective response rate was 80% (95% confidence interval [CI], 70%-88%), including 60% complete responses (95% CI, 49%-70%), reported L. Elizabeth Budde, MD, PhD, Division of Lymphoma, City of Hope Comprehensive Cancer Center, Duarte, CA, at the 2021 American Society of Hematology annual meeting.
The responses were durable, with a median duration of response of 22.8 months (95% CI, 9.7-not evaluable). The median progression-free survival was 17.9 months (95% CI, 10.1-not evaluable).
“We have seen deep and durable responses in heavily pretreated, high-risk relapsed or refractory follicular lymphoma patients with fixed-duration treatment,” said Dr Budde. “We also observed a very favorable tolerability profile, with most cytokine-release syndrome [CRS] 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 chimeric antigen receptor (CAR) T-cell therapy, mosunetuzumab can be infused directly into the bloodstream without removal and modification of the patient’s immune cells.
In June 2020, mosunetuzumab received breakthrough therapy designation by the FDA for the treatment of patients with relapsed or refractory follicular lymphoma after ≥2 lines of therapy.
“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,” Dr Budde said.
More than two-thirds (68.9%) of the patients had disease refractory to previous lines of therapy. Patients received a median of 3 previous lines of therapy, and 78.9% had disease refractory to a previous CD20-directed therapy.
Mosunetuzumab was administered intravenously in 21-day cycles with step-up dosing starting at 1 mg in cycle 1, to mitigate CRS. Patients with complete response by cycle 8 discontinued therapy; those with a partial response to therapy or stable disease continued treatment for a total of 17 cycles, until disease progression or unacceptable adverse events.
As of data cutoff (in August 27, 2021), the median follow-up was 18.3 months. The 60% complete response rate met the primary end point, and was significantly higher than the 14% historical rate (P <.0001), noted Dr Budde. The median time to first response was 1.4 months, and the median time to complete response was 3 months.
The response rates were similar across high-risk subgroups, including those with disease progression within 24 months of primary therapy and patients with double-refractory disease.
At 1 year, the event-free survival (EFS) rate was 62% among all responders and 76% among those with a complete response. The EFS rate was 57% at 18 months.
Most (92%) patients had at least 1 treatment-related adverse event, including 44.4% CRS. Most cases of CRS were grade 1 or 2 and occurred during the first cycle of treatment; the 2 cases of grade 3/4 CRS resolved with treatment. The median time to CRS onset was 5.2 hours in cycle 1 and 26.6 hours in subsequent cycles. The median duration of CRS was 3 days. The management of CRS consisted of corticosteroids in 10 patients and tocilizumab in 7.
The rate of neurologic adverse events was 4.4%, with no grade ≥3 events.
Only 4 of the 90 patients discontinued because of adverse events. Many were able to continue their normal daily routines throughout treatment, said Dr Budde.
The availability of CAR T-cell therapies and mosunetuzumab for patients with follicular lymphoma is a “win-win” for patients, Dr Budde said. “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.”
- Budde LE, Sehn LH, Matasar MJ, et al. Mosunetuzumab monotherapy is an effective and well-tolerated treatment option for patients with relapsed/refractory (R/R) follicular lymphoma (FL) who have received ≥2 prior lines of therapy: pivotal results from a phase I/II study. Blood. 2021;138(suppl 1):Abstract 127.