Multicenter phase 2 trial of tislelizumab plus zanubrutinib for Richter transformation

In patients with chronic lymphocytic leukemia, Richter transformation (RT) reflects the development of an aggressive lymphoma that is associated with poor response to chemotherapy and short survival. The multicenter phase 2 RT1 trial in Germany evaluated the combination of the PD-1 inhibitor tislelizumab and the BTK inhibitor zanubrutinib in patients with RT. Patients received the combination for 12 cycles; patients responding to treatment received maintenance therapy with both agents. The figure shows that response was seen in 28 out of 48 patients (58.3%; 95% CI 43.2-72.4) including complete response in 9 (18.8%), meeting the trials primary end point. Median duration of response was not reached during median 13.9 months follow-up. Median progression-free survival was 10.0 months (95% CI 3.8-16.3) and median overall survival was not reached with a 12-month overall survival rate of 74.7% (58.4-91.0). The most common adverse events were infections (18.0% of patients), gastrointestinal disorders (13.0%) and hematological toxicities (11.4%). The authors conclude that the combined checkpoint and BTK inhibition by tislelizumab and zanubrutinib is an effective and well-tolerated treatment strategy for patients with RT.