Background: For ELEVATE-TN (NCT02475681), we previously reported superior efficacy of acalabrutinib (A) ± obinutuzumab (O) vs O + chlorambucil (Clb) in patients (pts) with treatment-naive (TN) chronic lymphocytic leukemia (CLL) at 28.3 and 46.9 months (mo) median follow-up. Now, we report results from a 5-y update. Methods: Pts were randomized to A+O, A, or O+Clb. Pts who progressed on O+Clb could cross over to A monotherapy. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Results: A total of 535 pts (A+O, n=179; A, n=179; O+Clb, n=177) had a median age of 70 y. At a median follow-up of 58.2 mo (range, 0.0–72.0; data cutoff Oct 1, 2021), median PFS was not reached (NR) (hazard ratio [HR]: 0.11) for A+O and A (HR: 0.21) vs 27.8 mo for O+Clb (both P<0.0001). Estimated 60-mo PFS rates were 84% (A+O), 72% (A), and 21% (O+Clb). Median OS was NR in any treatment arm, and significantly longer in the A+O vs O+Clb arms (HR: 0.55; P=0.0474); estimated 60-mo OS rates were 90% (A+O), 84% (A), and 82% (O+Clb). ORR was significantly higher with A+O (96%; 95% CI 92–98) and A (90%; 85–94) vs O+Clb (83%; 77–88; P<0.0001 [A+O], P=0.0499 [A]). Complete response (CR)/CR with incomplete hematologic recovery (CRi) rates were higher with A+O (29%/3%) vs O+Clb (13%/1%); 13%/1% had CR/CRi with A; CR increased since the interim analysis (previously 21% [A+O] and 7% [A]). Adverse events (AEs) and treatment exposure are shown in the Table. Treatment is ongoing in 65% (A+O) and 60% (A) of pts; the most common reasons for treatment discontinuation were AEs (17% [A+O], 16% [A], 14% [O+Clb]) and progressive disease (6%, 10%, 2%, respectively). Crossover from O+Clb to A occurred in 72 (41%) patients; 25% of these pts discontinued A (10% due to AEs and 11% due to progressive disease). Conclusions: After a 5-y follow-up, efficacy and safety of A+O and A monotherapy were maintained, with significantly longer OS in the A+O arm compared with O+Clb. Clinical trial information: NCT02475681.

TE (treatment-emergent) AE: period from first dose to 30 days after last dose or start of new anticancer therapy, whichever is earlier.