Assessment of the Efficacy of Therapies Following Venetoclax Discontinuation in CLL Reveals BTK inhibition as an Effective Strategy.

Publication Date

2020

Journal Title

Clin Cancer Res

Abstract

PURPOSE:Venetoclax-based therapy is a standard of care option in front-line and relapsed/refractory CLL. Patient management following venetoclax discontinuation remains non-standard 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. Co-primary endpoints were overall response rate (ORR) and progression free survival (PFS) for the post-venetoclax treatments stratified by treatment type (BTKi, PI3Ki, and cellular therapies). RESULTS:We identified CLL patients who discontinued venetoclax in the front-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naïve (n=130), and 81% were idelalisib naïve (n=263). ORR to BTKi was 84% (n=44) in BTKi-naïve patients vs. 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 naïve 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 naïve or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies.

Volume Number

26

Issue Number

14

Pages

3589-3596

Document Type

Article

Status

Faculty

Facility

School of Medicine

Primary Department

General Internal Medicine

PMID

32198151

DOI

10.1158/1078-0432.ccr-19-3815

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