Fixed-duration (FD) ibrutinib (I) + venetoclax (V) for first-line (1L) treatment (tx) of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Three-year follow-up from the FD cohort of the phase 2 CAPTIVATE study.

Abstract

7519 Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of 1L I+V in CLL. The primary analysis (PA) evaluating FD tx with I+V was previously presented (Ghia et al., ASCO 2021). Here we present 3-y follow-up results from the FD cohort. Methods: Patients (pts) aged ≤70 y with previously untreated CLL/SLL received 3 cycles of I then 12 cycles of I+V (I 420 mg/d orally; V ramp-up to 400 mg/d orally). Responses were investigator assessed per iwCLL 2008 criteria. Undetectable minimal residual disease (uMRD; <10-4) was measured by 8-color flow cytometry. Serious AEs (SAEs) deemed related to I reported >30 d after last dose of study drug were collected. Results: 159 pts were enrolled (median age 60 y), including pts with high-risk features of del(17p)/ TP53 mutation (17%), unmutated IGHV (uIGHV; 56%), and complex karyotype (19%). 147 (92%) and 149 (94%) pts completed tx with I and V, respectively. With 1 y of additional follow-up since PA, median time on study was 39 mo (range 1-41). ORR was 96% and was consistent (96%-97%) in pts with high-risk features (Table).The primary endpoint of complete response (CR) including CR with incomplete bone marrow recovery (CRi) rate in pts without del(17p) (n=136) increased nominally from 56% (95% CI, 48-64) to 58% (95% CI 50-66); in all pts, CR rate increased from 55% (95% CI 48-63) to 57% (95% CI 50-65). In pts achieving CR, 93% had durable responses lasting ≥12 mo post-tx. Of pts with uMRD in peripheral blood at 3 mo post-tx, 66/85 (78%) evaluable pts maintained uMRD through 12-mo post-tx. At 36 mo, PFS was 88% (95% CI 82‒92) and OS was 98% (95% CI 94‒99); similar rates were seen in pts with high-risk features (Table). All pts are off tx; no new SAEs of any kind have occurred since the PA. Available data on relevant mutations in BTK, PLCɣ2, or BCL-2 at time of PD will be presented. As of January 2022, 12 pts were retreated with single-agent I after PD (tx duration range 3-29 mo); of evaluated pts, 7/9 had partial responses and 2/9 had stable disease. Conclusions: Fixed duration I+V continues to provide deep, durable responses and clinically meaningful PFS, including in pts with high-risk disease features, representing an all-oral, once-daily, chemotherapy-free FD regimen for previously untreated pts with CLL/SLL. With an additional 1 y of follow-up, no OS events or SAEs occurred. Manageable safety profile is unchanged as previously reported. To date, successful single-agent I retreatment responses are observed. Clinical trial information: NCT02910583. [Table: see text]