According to the results of a phase II study reported by Lynch et al in the Journal of Clinical Oncology, a chemotherapy-free approach using subcutaneous single-agent mosunetuzumab, or, for patients without an initial complete response, mosunetuzumab followed by polatuzumab vedotin plus obinutuzumab produced high response rates in previously untreated patients with follicular lymphoma or marginal zone lymphoma, both types of B-cell non Hodgkin lymphoma.
Study Details
Between March 2022 and October 2024, the investigator-initiated, open-label study enrolled 42 previously untreated adults with grade 1 to 2 or 3A follicular lymphoma or marginal zone lymphoma requiring therapy. The median patient age was 60 years (range = 36–83 years), 93% had stage III to IV disease, and 88% had follicular lymphoma. Symptomatic disease was an indication for treatment in 81% of patients.
Patients initially received eight 21-day cycles of subcutaneous mosunetuzumab, including step-up dosing during cycle 1. Response was assessed by computed tomography (CT) after four cycles and positron-emission tomography (PET)/CT after eight cycles. Patients achieving a complete response after eight cycles discontinued treatment. Those without a complete response could receive six additional cycles of obinutuzumab plus polatuzumab vedotin, followed by another PET/CT assessment. The primary endpoint was complete response rate at the end of all protocol-defined therapy; the secondary endpoint was overall response rate.
Key Results
At the end of treatment, the overall response rate was 100%, with 36 of 42 patients (86%) achieving a complete response, exceeding the protocol-defined benchmark of at least 80%. With mosunetuzumab alone, the overall response rate was 100% and the complete response rate was 71%. Twelve patients had a partial response after mosunetuzumab; of these, seven proceeded to obinutuzumab plus polatuzumab vedotin, and six completed all planned cycles and achieved a complete response. The remaining patient discontinued after one cycle because of toxicity and remained in partial response without further treatment.
At a median follow-up of 34 months, 2-year progression-free survival was 89% (95% confidence interval [CI] = 80%–100%), and 2-year overall survival was 100% (95% CI = 91%–100%). Four progression events occurred: two CD20-negative follicular lymphoma relapses and two biopsy-confirmed histologic transformations.
Exploratory circulating tumor DNA (ctDNA) analysis showed that, by the end of mosunetuzumab monotherapy, 93% (25 of 27) of patients with a complete response had undetectable ctDNA, whereas 67% (8 of 12) of those with a partial response continued to have detectable ctDNA (P = .0003).
Cytokine-release syndrome occurred in 64% of patients, but all events were grade 1. Infections occurred in 57%, and no treatment- or infection-related deaths were reported. Grade ≥ 3 hematologic adverse events included neutropenia in six patients and thrombocytopenia in two.
The investigators concluded: “Single-agent mosunetuzumab as well as response-adapted polatuzumab vedotin and obinutuzumab yield encouraging [complete response rates] and [progression-free survival] with limited toxicity among previously untreated patients with [follicular lymphoma] and [marginal zone lymphoma]. This chemotherapy-free strategy may provide a template for larger study designs for personalized approaches in this population that balances efficacy with safety.”
Ajay K. Gopal, MD, of the University of Washington and Fred Hutchinson Cancer Center, Seattle, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Roche/Genentech and Institute for Follicular Lymphoma Innovation. For full disclosures of the study authors, visit ascopubs.org.
