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

Richter's transformation (RT) to diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma arising from underlying chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL). RT is often chemorefractory, with resultant 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 (CRS) occurred in 65%, almost exclusively grade 1 (20%) or 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 (ORR) 40% and complete response rate (CR) 20%. CRs were durable, with 2 patients experiencing CR >20 months without further therapy, and 2 able to proceed to allogeneic stem cell transplant in CR, with no subsequent relapse. Median progression free and overall survival (PFS and OS) was 3.4 and 10.2 months respectively. Given the favorable toxicity profile of mosunetuzumab, and rapid and durable complete responses 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. NCT02500407.