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ATLANTA -- Use of the investigational bispecific antibody mosunetuzumab achieved deep and durable remissions in previously treated patients with relapsed/refractory follicular lymphoma, a researcher reported here.

In the phase I/II study in 90 pre-treated patients, 80% achieved an objective response (95% CI 70-88) with the therapy, while 60% (95% CI 49-70) had a complete response (CR), reported Elizabeth Budde, MD, PhD, of City of Hope in Duarte, California.

Response was also durable, with a median duration of response (DoR) of 22.8 months (95% CI 9.7-not evaluable).

"This is the first T-cell-engaging bispecific antibody to demonstrate clinically meaningful outcomes for patients with relapsed/refractory follicular lymphoma in a pivotal phase II setting," said Budde at a press briefing at the American Society of Hematology annual meeting.

Budde explained that follicular lymphoma is characterized by frequent relapses, with response rates and DoR that decline with successive lines of treatment. Disease progression within 2 years (POD24), as well as refractory disease, are particularly associated with poor outcomes.

Mosunetuzumab is a bispecific CD20xCD3 antibody that engages and redirects T cells to eliminate CD20-positive malignant B cells. Unlike CAR T-cell therapy, it can be infused directly into the bloodstream without requiring the removal and modification of patients' immune cells. The agent received in 2020.

"Mosunetuzumab, whether given intravenously or subcutaneously, is available off-the-shelf, because it is already pre-made, and ready whenever the patient is ready to use it," Budde pointed out.

In the dose escalation phase of this trial, the drug was found to be highly active in relapsed/refractory follicular lymphoma patients who had received two or more previous lines of therapy, including at least one anti-CD 20 antibody treatment and one alkylating agent.

In the current study, IV mosunetuzumab was given in 21-day cycles, with step-up dosing in cycle 1 for the mitigation of cytokine release syndrome (CRS). Patients who achieved a CR by cycle 8 discontinued therapy, while those with a partial response or stable disease continued treatment for a total of 17 cycles, unless there was disease progression or unacceptable toxicity.

The primary endpoint was CR, as assessed by independent review in comparison with a 14% historical CR rate, and objective response rate (ORR), as well as DoR.

Budde noted that the 60% CR demonstrated in this study was significantly higher than the historical control (P<0.0001).

She also observed that response rates were comparable across high-risk subgroups, including POD24 (CR 57%, 95% CI 42-72; ORR 85%, 95% CI 72-94) and double-refractory patients (CR 50%, 95% CI 35-65; ORR 71%, 95% CI 56-83). In addition, the median time to first response was 1.4 months (95% CI 1.1-8.9), while median time to first CR was 3.0 months (95% CI 1.1-18.9), and median progression-free survival was 17.9 months (95% CI 10.1-not evaluable).

CRS was reported in 40 (44%) of patients, but the vast majority of cases were grade 1 or 2 and occurred in cycle 1 of treatment; all cases of CRS eventually resolved.

Budde reported that the therapy's safety profile was manageable, with adverse events leading to therapy discontinuation in 4.4% of patients, and 2.2% related to mosunetuzumab.

When asked what role CAR T-cell therapies and mosunetuzumab will play in terms of sequencing and managing patients with follicular lymphoma, Budde said it's a "win-win" for patients.

"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," she said. If mosunetuzumab is approved, "I think a good discussion with patients about the pros and cons of each one is definitely warranted," she stated.

ASH press briefing moderator, and trial co-investigator, Laurie S. Sehn, MD, MPH, said that bispecifics have the potential to make a real impact on patients with follicular lymphoma.

"I think that for many of the lymphomas, it really is an evolving treatment paradigm and many of us suspect that bispecifics will make their way into the clinical realm relatively shorter for follicular lymphoma," said Sehn, who is from the University of British Columbia in Vancouver.

"Right now the upfront treatment for follicular lymphoma relies very much on chemoimmunotherapy," she added. "I would say there is no real standard of care worldwide in the second-line setting, but the move towards non-chemotherapy approaches is likely where we will see treatment for follicular lymphoma going. We've seen it already for chronic lymphocytic leukemia where chemoimmunotherapy has been pushed back, if used at all, in many patients."

"With innovative treatments like we're seeing today with mosunetuzumab, and the efficacy we are seeing, I have no doubt that trials that are currently enrolling patients are likely to see the same paradigm shift for follicular lymphoma, and truly rely on non-chemotherapy approaches in the future," Sehn noted.

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