期刊
CLINICAL CANCER RESEARCH
卷 26, 期 14, 页码 3589-3596出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-19-3815
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资金
- NIH/NCI Cancer Center Support Grant [P30 CA008748]
Purpose: Venetoclax-based therapy is a standard-of-care option in first-line and relapsed/refractory chronic lymphocytic leukemia (CLL). Patient management following venetoclax discontinuation remains nonstandard and poorly understood. Experimental Design: To address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetoclax and have been subsequently treated. Coprimary endpoints were overall response rate (ORR) and progression-free survival for the post-venetoclax treatments stratified by treatment type [Bruton's tyrosine kinase inhibitor (BTKi), PI3K inhibitor (PI3Ki), and cellular therapies]. Results: We identified patients with CLL who discontinued venetoclax in the first-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naive (n = 130), and 81% were idelalisib naive (n = 263). ORR to BTKi was 84% (n = 44) in BTKi-naive patients versus 54% (n = 30) in BTKi-exposed patients. We demonstrate therapy selection following venetoclax requires prior novel agent exposure consideration and discontinuation reasons. Conclusions: For BTKi-naive patients, selection of covalently binding BTKis results in high ORR and durable remissions. For BTKi-exposed patients, covalent BTK inhibition is not effective in the setting of BTKi resistance. PI3Kis following venetoclax do not appear to result in durable remissions. We conclude that BTKi in naive or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies.
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