Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory Richter transformation

ABSTRACT: Richter transformation (RT) to diffuse large B-cell lymphoma is an aggressive lymphoma that arises from underlying chronic lymphocytic leukemia or small lymphocytic lymphoma. RT is often chemorefractory, resulting in poor clinical outcomes with standard chemoimmunotherapy. Mosunetuzumab, a bispecific CD20/CD3 T-cell-engaging antibody, was investigated in a cohort of 20 patients with relapsed/refractory RT. Cytokine release syndrome occurred in 65% of patients, almost exclusively grade 1 (20%) or grade 2 (40%), and occurring during the first treatment cycle. Other adverse events included infections, neutropenia, thrombocytopenia, tumor flare, and low-grade neurotoxicity, with no adverse events leading to treatment discontinuation. Mosunetuzumab resulted in an overall response rate of 40% and a complete response (CR) rate of 20%. CRs were durable, with 2 patients experiencing CR for >20 months without further therapy, and 2 were able to proceed to allogeneic stem cell transplant while in CR, with no subsequent relapse. Median progression-free survival and overall survival were 3.4 and 10.2 months, respectively. Given the favorable toxicity profile of mosunetuzumab and rapid and durable CRs observed in this cohort, further investigation of mosunetuzumab for the treatment of RT, as monotherapy and in combination with other novel agents or chemotherapy, is warranted. This trial was registered at www.ClinicalTrials.gov as NCT02500407.