Mosunetuzumab, a bispecific antibody against CD3 and CD20, followed by response-adapted polatuzumab vedotin and obinutuzumab provided encouraging complete response (CR) rates and progression-free survival (PFS) for patients with untreated indolent B-cell non-Hodgkin lymphomas in a single-arm phase 2 trial.
The investigators, led by Ryan C Lynch, MD, of Fred Hutchinson Cancer Center in Seattle, Washington, published their findings in the Journal of Clinical Oncology.
The study enrolled 42 patients with previously untreated follicular lymphoma or marginal zone lymphoma. The cohort had a median age of 60 years (range, 36-83), 39 had stage III to IV disease, 37 had follicular lymphoma, and 13 had tumor bulk over 7 cm. All patients received eight cycles of mosunetuzumab, and those who did not achieve a CR could go on to receive six cycles of polatuzumab vedotin and obinutuzumab.
At the end of treatment, the overall response rate (ORR) was 100% and the CR rate was 86% with mosunetuzumab and response-adapted polatuzumab vedotin and obinutuzumab. The ORR and CR rate with mosunetuzumab alone were 100% and 71%, respectively. After a median follow-up of 34 months, the two-year PFS rate was 89% (95% CI, 80-100) and the two-year overall survival rate was 100%. Four progression events occurred, including two cases each of CD20 loss and histologic transformation. A total of 27 patients had cytokine release syndrome, but all were grade 1 and no patients required tocilizumab.
“This chemotherapy-free strategy may provide a template for larger study designs for personalized approaches in this population that balances efficacy with safety,” wrote Dr. Lynch and colleagues.
Reference
Lynch RC, Poh C, Shadman M, et al. Mosunetuzumab with response-adapted polatuzumab vedotin and obinutuzumab in untreated indolent B-cell non-Hodgkin lymphoma. J Clin Oncol 0, JCO-25-02906. https://doi.org/10.1200/JCO-25-02906
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