A Multicenter Study of Venetoclax-Based Treatment for Patients With Richter Transformation of Chronic Lymphocytic Leukemia

Authors

Paul J Hampel
Mahesh Swaminathan
Kerry A Rogers
Erin M Parry
Jan A Burger
Matthew S Davids
Wei Ding
Alessandra Ferrajoli
Jonathan M Hyak
Nitin Jain
Saad S Kenderian
Yucai Wang
William G Wierda
Jennifer A Woyach
Sameer A Parikh
Philip A Thompson

Publication Date

5-28-2024

Journal

Blood Advances

Abstract

Patients 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 BCL2 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 (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and 52%/38%, respectively. The median progression-free and overall survival estimates for the same treatment groups were 4.9/14.3 months, 14.9 months/not reached, and 3.3/9 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=0.01) and venetoclax-naïve subgroup (OR 0.13; 95%CI 0.02-0.66; p=0.01). TP53 mutated CLL was associated with a lower complete response rate (OR 0.15; 95%CI 0.03-0.74; p=0.02) and shorter progression-free survival (hazard ratio 3.1; 95%CI 1.21-7.95; p=0.02) only in 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 RT patient population, venetoclax-based combination regimens achieved high response rates, with durable remission and survival observed in a subset of patients.

Keywords

Humans, Bridged Bicyclo Compounds, Heterocyclic, Sulfonamides, Leukemia, Lymphocytic, Chronic, B-Cell, Aged, Female, Male, Middle Aged, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, Retrospective Studies, Adult, Treatment Outcome, Cyclophosphamide, Rituximab, Doxorubicin, Vincristine

Comments

Supplementary Materials

PMID: 38537065