LAUSR

Background: CAPTIVATE (NCT02910583) is a multicenter phase 2 study of first-line ibrutinib (Ibr) + venetoclax (Ven) in CLL. In the Minimal Residual Disease (MRD) cohort, pts underwent randomization to subsequent treatment based on MRD status after completing Ibr + Ven (Wierda et al, J Clin Oncol 2021). Here, 4-yr follow-up (3-yr post-randomization) outcomes are reported for MRD cohort pts randomized to continued Ibr or Ibr + Ven. Methods: 164 pts aged <70 yr with previously untreated CLL received 3 cycles of Ibr then 12 cycles of Ibr + Ven (Ibr 420 mg/d; Ven ramp-up to 400 mg/d); a 13th cycle occurred concurrent with MRD assessment. Pts not meeting criteria for Confirmed undetectable MRD (uMRD Not Confirmed) were randomized to open-label Ibr (n=31) or Ibr + Ven (n=32; 1 additional yr of Ibr + Ven then Ibr alone). Pts with Confirmed uMRD were randomized 1:1 to double-blind placebo or Ibr (n=86). Results: In uMRD Not Confirmed pts, median time on study was 48 mo; post-randomization median follow-up was 33 mo. Improvements in overall best uMRD rates from pre-randomization were: +3% (to 48%) with Ibr and +25% (to 72%) with Ibr + Ven in peripheral blood, and +10% (to 42%) with Ibr and +38% (to 69%) with Ibr + Ven in bone marrow. uMRD rates over time are in the Table. Improvements in complete response (CR) rates were similar with Ibr (+29%) and Ibr + Ven (+28%). 4-yr progression-free survival (PFS) rates were 93% in both arms; 4-yr overall survival (OS) rates were 97% (Ibr) and 100% (Ibr + Ven) and consistent with Confirmed uMRD arms (Allan et al, ASH 2022). Adverse events (AEs) generally decreased over time post-randomization (Table) except for hypertension. In this 4th yr of follow-up (25-36 mo post-randomization), atrial fibrillation was rare (n=1/arm); no AEs led to drug discontinuation in either arm. With continued Ibr, outcomes in uMRD Not Confirmed pts were similar to those in Confirmed uMRD pts: median time on study, 56 mo; post-randomization median follow-up, 42 mo; CR rate, 81%; 4-yr PFS, 95%; 4-yr OS, 98%. Conclusion: In pts without Confirmed uMRD after Ibr + Ven, continued Ibr + Ven improved uMRD rates; PFS and OS were similarly high with continued Ibr or Ibr + Ven (≥97%). AE rates generally decreased over time in both arms. Outcomes with continued Ibr were not impacted by pre-randomization Confirmed uMRD status. Table. uMRD rates and prevalence of AEs over time in uMRD Not Confirmed pts Ibr + Ven then Ibr Ibr + Ven then Ibr + Ven uMRD rate at selected timepoints in evaluable pts, n/N (%) End of Pre-Rnd 12 cycles Post-Rnd 36 cycles Post-Rnd End of Pre-Rnd 12 cycles Post-Rnd 36 cycles Post-Rnd Peripheral blood 13/31 (42) 10/31 (32) 7/31 (23) 9/32 (28) 19/30 (63) 11/31 (35) Bone marrow 10/31 (32) 9/30 (30) Not done 10/31 (32) 18/31 (58) Not done Prevalence of AEs of clinical interest, n (%)a First 16 cycles, n=31 1-12 mo, n=31 25-36 mo, n=27 First 16 cycles, n=32 1-12 mo, n=32 25-36 mo, n=25 Grade ≥3 AEs Hypertension 2 (6) 1 (3) 0 2 (6) 0 0 Atrial fibrillation 1 (3) 0 0 0 1 (3) 0 Diarrhea 2 (6) 0 0 2 (6) 1 (3) 0 Neutropenia 10 (32) 2 (6) 0 10 (31) 2 (6) 0 Infections/infestations 6 (19) 0 2 (7) 2 (6) 2 (6) 1 (4) Hemorrhage 0 0 0 0 1 (3) 0 Any-grade AEs Hypertension 5 (16) 5 (16) 6 (22) 5 (16) 4 (13) 5 (20) Atrial fibrillation 3 (10) 2 (6) 1 (4) 0 2 (6) 1 (4) aAEs were assessed at every visit pre-Rnd and every 3 cycles post-Rnd. Rnd, randomization. Citation Format: Tanya Siddiqi, Constantine S. Tam, William G. Wierda, Paolo Ghia, Thomas J. Kipps, Alessandra Tedeschi, Eva Gonzalez-Barca, Edith Szafer-Glusman, Cathy Zhou, Lynne D. Neumayr, John N. Allan. Similar outcomes regardless of post-randomization treatment with ibrutinib or ibrutinib + venetoclax in the phase 2 CAPTIVATE study of first-line ibrutinib + venetoclax in CLL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT166.