An Emerging Option for Treatment of Richter Transformation

Diffuse large B-cell lymphoma (DLBCL) arising in patients with preexisting chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), designated as Richter transformation, is associated with poor response and short survival following immunochemotherapy. Investigators now report a prospective, multicenter, phase 2 trial of the programmed cell death-ligand 1 (PD-L1) inhibitor atezolizumab (A), the BCL2 inhibitor venetoclax (V), and the anti-CD20 antibody obinutuzumab (O) in patients with documented CLL/SLL, biopsy-proven DLBCL, no prior treatment with study agents, and no prior DLBCL-directed therapy. Patients received AVO in cycles 1 to 8, AV in cycles 9 to 18, and single-agent V in cycles 19 to 35.

Among the key findings:

• Of the 28 patients enrolled, 19 (67.9%) achieved partial or complete response by the end of AVO cycle 6 (the primary endpoint); four patients progressed before cycle 6 and two did not achieve response at cycle 6 restaging.
• Nineteen patients continued therapy, with six completing cycle 35.
• With a median follow-up of 16.8 months, the 12-month progression-free survival was 42.9% and overall survival 64.3%; 8 of 19 responding patients had ongoing response at 24 months.
• Toxicities included neutropenia and five treatment-related infections (two fatal due to sepsis and fungal pneumonia). Six patients (21%) had immune-related adverse events, but none required treatment discontinuation; no tumor lysis syndrome occurred.