Patricia F. Walker, Ann Janssens, George A Follows, Ian W. Flinn, Karin Karlsson, Miklos Egyed, Min Hui Wang, Talha Munir, Paolo Ghia, Steven Coutre, Renata Walewska, Laura Fogliatto, Emmanuelle Ferrant, Priti Patel, Florence Cymbalista, Jeff P. Sharman, Veerendra Munugalavadla, Jennifer A. Woyach, William G. Wierda, Versha Banerji, Manali Kamdar, Alan P Skarbnik, Gillian Corbett, Yair Herishanu, Wojciech Jurczak, John M. Pagel, and John C. Byrd
Context: Results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 months demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in TN CLL (Sharman et al. Lancet 2020;395:1278-91). Objective: To report the results from a 4-year update of ELEVATE-TN. Design: Randomized, multicenter, open-label, 3-arm, Phase 3 study. Patients: TN CLL. Interventions: Patients received A±O or O+Clb. Crossover to A monotherapy was permitted in patients who progressed on O+Clb. Main Outcome Measures: Investigator-assessed (INV) progression-free survival PFS, INV ORR, OS, and safety were evaluated. Results: 535 patients (A+O, n=179; A, n=179; O+Clb, n=177) were randomized with a median age of 70 y; 14% had del(17p) and/or mutated TP53. At a median follow-up of 46.9 months (range, 0.0–59.4; data cutoff: Sept 11, 2020), median PFS was not reached (NR) for A+O and A patients vs 27.8 months for O+Clb patients (both P Conclusions: With a median follow-up of 46.9 months (~4y), the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.