A multicenter study of venetoclax-based treatment for patients with Richter transformation of chronic lymphocytic leukemia

Abstract

AbstractPatients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a B-cell lymphoma 2 protein inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (n = 28), R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; n = 13), or intensive chemoimmunotherapy other than R-CHOP (n = 21). The best overall and complete response rates were 36% and 25%, 54% and 46%, and 52% and 38%, respectively. The median progression-free and overall survival estimates for the same treatment groups were 4.9 and 14.3 months, 14.9 months and not reached, and 3.3 and 9 months, respectively. CLL with del(17p) was associated with a lower complete response rate in the total cohort (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.04-0.6; P = .01) and venetoclax-naïve subgroup (OR, 0.13; 95% CI, 0.02-0.66; P = .01). TP53-mutated CLL was associated with a lower complete response rate (OR, 0.15; 95% CI, 0.03-0.74; P = .02) and shorter progression-free survival (hazard ratio, 3.1; 95% CI, 1.21-7.95; P = .02) only in the venetoclax-naïve subgroup. No other clinical or baseline characteristics, including prior venetoclax treatment for CLL, showed statistically significant association with outcomes. Grade 3/4 neutropenia and thrombocytopenia events were most frequent with intensive chemoimmunotherapy + venetoclax; grade 3/4 infection rates were similar across treatment groups. In this difficult-to-treat patient population with RT, venetoclax-based combination regimens achieved high response rates, with durable remission and survival observed in a subset of patients.