威尼斯人
化学免疫疗法
医学
内科学
慢性淋巴细胞白血病
危险系数
胃肠病学
中性粒细胞减少症
伊布替尼
肿瘤科
白血病
置信区间
化疗
作者
Paul J. Hampel,Mahesh Swaminathan,Kerry A. Rogers,Erin M. Parry,Jan A. Burger,Matthew S. Davids,Wei Ding,Alessandra Ferrajoli,Jonathan Hyak,Nitin Jain,Saad S. Kenderian,Yucai Wang,William G. Wierda,Jennifer A. Woyach,Sameer A. Parikh,P. A. Thompson
出处
期刊:Blood Advances
[American Society of Hematology]
日期:2024-03-27
标识
DOI:10.1182/bloodadvances.2023012080
摘要
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), 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.
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