Outcomes in high-risk subgroups after fixed-duration ibrutinib + venetoclax for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Up to 5.5 years of follow-up in the phase 2 CAPTIVATE study.

• DOI: 10.1200/jco.2024.42.16_suppl.7009
• Publication Date: 2024-06-28T20:19:52Z
• Authors: William G. Wierda; Ryan Jacobs; Paul M. Barr; John N. Allan; Tanya Siddiqi; Alessandra Tedeschi; Thomas J. Kipps; Susan Mary O'Brien; Xavier C. Badoux; Andrea Visentin; Masa Lasica; Dennis Carney; Anna Elinder Camburn; Javier De La Sern...; Edith Szafer-Glusman; Cathy Zhou; Anita Szoke; James P. Dean; Paolo Ghia; Constantine S. Tam
• Keywords: Venetoclax; IGHV@

7009 Background: The phase 2 CAPTIVATE study evaluated first-line ibrutinib (Ibr) + venetoclax (Ven) for CLL/SLL in cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). Ibr±Ven retreatment was allowed patients (pts) who had progressive (PD). Here, we report outcomes pts with high-risk genomic features from the FD cohort MRD placebo arm. Methods: Pts aged ≤70 y previously untreated without restriction on risk factors received 3 cycles of Ibr, then 12 Ibr+Ven (Ibr, 420 mg/d orally; Ven, 5-wk ramp up to 400 orally). On-study included single-agent Ibr or arm); PD >2 after end treatment (EOT) could be retreated Results: In (n=159) a median follow-up 61.2 mo (range, 0.8–66.3), 5-y PFS OS rates (95% CI) were 67% (59–74) 96% (91–98), respectively. higher undetectable at EOT peripheral blood (83%) bone marrow (84%) vs those (48% 50%, respectively). were: del(17p)/mutated TP53 41% (21–59), complex karyotype 57% (37–72), del(11q) 64% (30–85), unmutated IGHV 68% (50–80) (Table). total, 18 second malignancies occurred 13 (10 events 8 during Ibr+Ven, 6 4 before retreatment, retreatment). Of 202 completed cohort, n=159; arm, n=43), 63 have date; 43/63 (68%). 32/63 (51%) initiated (n=25) (n=7). With time 21.9 0.03–50.4), ORR 86% 22 evaluable (best response: 1 CR; nodular PR; 17 SD; [Richter transformation]). 13.8 3.7–15.1), 71% 7 PR lymphocytosis; SD). Conclusions: 5.5 follow-up, continues provide clinically meaningful features, as well overall population. Ibr-based provides promising responses needing subsequent therapy all-oral regimen Ibr+Ven. Clinical trial information: NCT02910583 . [Table: see text]