The bispecific antibody mosunetuzumab achieved deep and durable remissions as monotherapy in patients with relapsed or refractory follicular lymphoma who had received two or more prior lines of therapy, according to pivotal results of a phase I/II trial presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition by L. Elizabeth Budde, MD, PhD, and colleagues (Abstract 127). In the single-arm study, 80% of patients responded to mosunetuzumab and 60% experienced a complete remission—much higher rates than achieved by other treatments in this setting.
“This is a very efficacious, very safe drug, even for subgroups of patients who typically do not respond well to existing therapies,” said Dr. Budde, of City of Hope Comprehensive Cancer Center, who presented the results in a press conference at the meeting. “The results are a strong endorsement of the unique mechanism of action for this drug.”
L. Elizabeth Budde, MD, PhD
Laurie H. Sehn, MD, MPH
These results for an off-the-shelf T-cell engager were hailed as “potentially transformative” and “shifting the paradigm” by press conference moderator Laurie H. Sehn, MD, MPH, of the University of British Columbia in Vancouver.
“With the efficacy of mosunetuzumab, I have no doubt that ongoing trials will show the same paradigm shift for follicular lymphoma and rely on nonchemotherapy approaches in the future. For someone who has spent her career giving chemotherapy for follicular lymphoma, this new era of therapy is so exciting,” added Dr. Sehn.
Follicular lymphoma is characterized by recurrent relapses, and both the response and duration of response decrease with each successive treatment line, typically with more chemotherapy. Mosunetuzumab is a bispecific antibody that engages and redirects T cells to eliminate malignant B cells.
“By contrast with chimeric antigen receptor T-cell therapy, [mosunetuzumab] is an off-the-shelf product with a fixed duration of treatment. It’s one and done," explained Dr. Budde.
Study Details
Dr. Budde reported results from a large expansion cohort of patients who received mosunetuzumab in 21-day cycles at recommended phase II step-up dosing (1/2/60/30 mg). The cohort included 90 patients with grade 1 to 3A follicular lymphoma treated with at least two prior regimens, including an anti–CD20-antibody and at least one alkylating agent. If a patient achieved a complete response after eight cycles, therapy was stopped. Those with a partial response or stable disease at cycle 8 could get up to 17 cycles of mosunetuzumab.
Median age was 60 years (range = 29–90), and the median number of prior therapies received was three (range = 2–10). More than three-quarters of patients (78.9%) were refractory to any prior anti–CD20 therapy.
At a median follow-up of 18 months, the objective response rate (the primary endpoint) was 80%, and complete response rate was 60%, “which is higher than historical complete response rates with other therapies in the relapsed/refractory setting,” Dr. Budde told listeners.
“One year after treatment, more than 60% of those who responded and 76% of those with a complete response experienced no complications or cancer progression,” she added.
A waterfall plot showed that nearly all patients achieved some degree of response. Responses were achieved across all subgroups. The duration of response in those who responded was 22.8 months, and median progression-free survival was 17.9 months.
This pivotal phase II study of mosunetuzumab met the primary endpoint with a complete response rate of 60%. This is the first T-cell–engager bispecific antibody to demonstrate high responses in relapsed/refractory follicular lymphoma, and it is a promising off-the-shelf therapy.— L. Elizabeth Budde, MD, PhD
Tweet this quote
Mosunetuzumab had a manageable safety profile, and patients did not require hospitalization. Adverse events leading to discontinuation were uncommon. Cytokine-release syndrome occurred in 44.4% of patients, but all except two cases were classified as low grade, and all cases were manageable and reversible.
“This pivotal phase II study of mosunetuzumab met the primary endpoint with a complete response rate of 60%. This is the first T-cell–engager bispecific antibody to demonstrate high responses in relapsed/refractory follicular lymphoma, and it is a promising off-the-shelf therapy,” Dr. Budde stated.
“The goal is not only to treat the lymphoma, but to improve the quality of life for patients. By motivating our immune system to recognize lymphoma cells, this drug could give us an opportunity for chemotherapy-free treatment for follicular lymphoma,” Dr. Budde stated.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
