Abstract CT028: Fixed-duration (FD) ibrutinib (Ibr) + venetoclax (Ven) for first-line treatment of chronic lymphocytic leukemia (CLL) in patients (pts) with high-risk features: phase 2 CAPTIVATE study

Abstract Background: CAPTIVATE (PCYC-1142; NCT02910583) is an international, multicenter phase 2 study of first-line Ibr + Ven in CLL with 2 cohorts: the Minimal Residual Disease (MRD) and FD cohorts. FD Ibr + Ven provides deep, durable responses (Ghia, ASCO 2021; Wierda, J Clin Oncol 2021). Here, we report efficacy and safety of FD Ibr + Ven in pts with high-risk features. Methods: Pts aged ≤70 y with previously untreated CLL received 3 cycles of Ibr then 12 cycles of Ibr + Ven (Ibr 420 mg/d orally; Ven ramp-up to 400 mg/d orally). Pts in the FD cohort received no further treatment. Pts in the MRD cohort were randomized to subsequent treatment according to MRD status, including a placebo arm for pts who achieved confirmed undetectable MRD (uMRD) with 12 cycles of Ibr + Ven. Data from the FD cohort and MRD cohort placebo arm were pooled for pts with high-risk features (del(17p), TP53 mutated, or unmutated IGHV) treated with FD Ibr + Ven. Results: Of 202 pts treated with FD Ibr + Ven in the FD cohort (n=159) or MRD cohort placebo arm (n=43), 129 pts had high-risk features (Table). Median time on study for these pts was 28.7 mo (range 0.8-45.1). 94% of pts completed planned treatment with Ibr and Ven. Median treatment duration was 13.8 mo (range 0.7-24.9) for Ibr and 11.1 mo (range 9.9-22.1) for Ven. Best response rates of CR and uMRD in peripheral blood and bone marrow were high (Table). The 18-mo landmark estimate for duration of CR was 95%. 24-mo PFS rate was 94%, which was similar to pts without high-risk features (97%). Only 3% of pts discontinued Ibr or Ven due to AEs. The AE profile of Ibr + Ven in pts with high-risk features showed no new safety findings for this FD regimen (Table). Conclusion: First-line Ibr + Ven for a fixed duration provides durable treatment-free remissions and sustained PFS in pts with CLL. These clinical outcomes are maintained in pts with high-risk features, with PFS rates that were similar to pts without high-risk features. Table. Baseline characteristics, efficacy outcomes, and safety Pts with high-risk features (n=129) BASELINE CHARACTERISTICS Median age, y (range) 60 (33-70) Rai stage III/IV, n (%) 36 (28) Bulky disease ≥5 cm, n (%) 47 (36) Genomic risk features, n (%) del(17p) and/or TP53 mutated 29 (22) Unmutated IGHV 119 (92) Complex karyotypea 27 (21) EFFICACY OUTCOMES Overall response rate, n (%) 126 (98) CR, n (%) 76 (59) 18-mo DOCR, % (95% CI) 95 (85-98) uMRD <10-4 by flow, n (%) Peripheral blood 114 (88) Bone marrow 93 (72) 24-mo PFS rate, % (95% CI) 94 (88-97) 24-mo OS rate, % (95% CI) 98 (93-99) SAFETY OUTCOMES Grade 3/4 AEs in ≥5% of pts, n (%) Neutropenia 38 (29) Hypertension 12 (9) Neutrophil count decreased 9 (7) aDefined as ≥3 abnormalities by CpG-stimulated cytogenetics. Citation Format: John N. Allan, Ian W. Flinn, Tanya Siddiqi, Paolo Ghia, Constantine S. Tam, Thomas J. Kipps, Paul M. Barr, Anna Elinder Camburn, Alessandra Tedeschi, Xavier C. Badoux, Ryan Jacobs, Bryone J. Kuss, Livio Trentin, Cathy Zhou, Anita Szoke, Maoko Naganuma, William G. Wierda. Fixed-duration (FD) ibrutinib (Ibr) + venetoclax (Ven) for first-line treatment of chronic lymphocytic leukemia (CLL) in patients (pts) with high-risk features: phase 2 CAPTIVATE study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT028.