Watch our interview with Stephen J. Schuster, MD.
The bispecific monoclonal antibody mosunetuzumab, which binds to CD3 and CD20, led to durable responses in patients with B-cell non-Hodgkin lymphoma (NHL), even in those who had disease that was relapsed or refractory to chimeric antigen receptor (CAR) T-cell therapy. Stephen J. Schuster, MD, from the University of Pennsylvania, presented these results as a plenary abstract at the 2019 ASH Annual Meeting.
Unlike the two FDA−approved CAR T-cell therapies for lymphoid neoplasms, which need to be manufactured for individual patients (a process that currently requires several weeks), mosunetuzumab is available “off the shelf.” Eliminating this potential treatment delay will be important for some patients with poor-prognosis B-cell NHL, Dr. Schuster noted.
This dose-escalation trial enrolled patients with B-cell NHL who had received at least 1 prior therapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and for whom there was “no available therapy that would be expected to improve survival,” Dr. Schuster said. Patients who received CAR T-cell therapy within 30 days of
enrollment or who had undergone allogeneic hematopoietic cell transplantation were excluded.
A total of 270 patients (median age = 62 years; range = 19-96) were enrolled and evaluable for safety. Most (n=164; 61.2%) had an ECOG performance status of 1 and were considered to have aggressive NHL (n=180; 66.7%). The most common diagnosis was diffuse large B-cell lymphoma (DLBCL; n=117, 43.3%), followed by transformed follicular lymphoma (FL; n=32, 11.9%). Participants had received a median of 3 prior systemic therapies (range = 1-14).
Dr. Schuster highlighted the 30 patients who had received prior CAR T-cell therapy: 17 with DLBCL, 8 with transformed FL, and 5 with FL. This patient subset had heavily pretreated disease, with a median of 5 prior lines of therapy (range = 3-14). Another 77 patients had progressive disease after undergoing an autologous hematopoietic cell transplantation.
Per study protocol, mosunetuzumab was administered with step-up dosing on days 1, 8, and 15 of cycle 1, followed by fixed doses on day 1 of each 21-day cycle, for up to 17 cycles. Patients who achieved a complete remission (CR) after the first 8 cycles stopped therapy, while those with a partial response or stable disease continued treatment for the full 17 cycles.
Treatment with single-agent mosunetuzumab appeared to “generate long-lasting responses with a very tolerable safety profile in patients with B-cell NHLs for whom multiple prior treatments have failed and whose prognosis is poor,” Dr. Schuster said. In the group of 124 patients with aggressive NHL who received mosunetuzumab in doses ranging from 2.8 mg to 40.5 mg, the objective response rate (ORR) was 37.1%, with a CR rate of 19.4%. CRs appeared to be durable, with 17 of 24 patients remaining in CR for up to 16 months after stopping treatment. Similar response rates and durability were seen in the group with indolent NHLs (who received mosunetuzumab at doses ranging from 2.8 mg to 13.5 mg): ORR was 62.7% and CR rate was 43.3%.
In addition, in the subgroup who had previously received CAR T-cell therapy, the ORR was 39% and the CR rate was 22%.
Dr. Schuster also reported that, in the 4 patients whose disease relapsed after an initial CR, 3 responded to repeat treatment with mosunetuzumab, including 1 CR. This further sets the agent apart from CAR T-cell therapies, he said, since patients who have relapsed after CAR-T cell therapies do not commonly respond to the same therapy administered again.
Commenting on the observed safety profile of mosunetuzumab, Dr. Schuster reported that the adverse events (AEs) seen with the bispecific antibody were similar to those typically observed with CAR T-cell therapies. This included cytokine release syndrome (CRS) in 78 patients (28.9%); most of these events (96.2%) were grade 1 or 2 in severity. Most CRS events also occurred during the first treatment cycle and were resolved by the clinical cutoff date of August 9, 2019.
Neurologic toxicity, another common concern with CAR T-cell therapy, occurred in 43.7% of patients (n=118). The most common neurologic AEs were headache (15.6%), insomnia (9.3%), and dizziness (9.3%). Again, most of these AEs were low-grade. The safety profile was similar in the subgroup of CAR T-cell–treated patients, Dr. Schuster added.
The findings of this trial are limited by its single-arm design, and Dr. Schuster said that he is eager to see the durability of remissions at longer-term follow-up. Mosunetuzumab continues to be studied as a single-agent and as part of combined treatment in ongoing clinical trials, including those enrolling patients with previously untreated DLBCL.
Study authors reported relationships with Genentech, which sponsored the trial.
Schuster SJ, Bartlett NL, Assouline S, et al. Mosunetuzumab induces complete remissions in poor prognosis non-Hodgkin lymphoma patients, including those who are resistant to or relapsing after chimeric antigen receptor T-cell (CAR-T) therapies, and Is active in treatment through multiple lines. Abstract #6. Presented at the 2019 ASH Annual Meeting, December 8, 2019; Orlando, FL.