Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN

Sharman, J. P.; Egyed, M.; Jurczak, W.; Skarbnik, A.; Patel, K.; Flinn, I. W.; Kamdar, M.; Munir, T.; Walewska, R.; Hughes, M.; Fogliatto, L. M.; Herishanu, Y.; Banerji, V.; Follows, G.; Walker, P.; Ghia, P.; Janssens, A.; Byrd, J. C.; Ferrant, E.; Ferrajoli, A.; Wierda, W. G.; Wachira, C. W.; Suterwala, B. T.; Miranda, P.; Munugalavadla, V.; Wun, C. -C.; Woyach, J. A.

doi:10.1182/blood.2024024476

Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia. We present results from ELEVATE-TN after a median follow-up of 74.5 months. Overall, 535 patients were randomized (acalabrutinib-obinutuzumab, n = 179; acalabrutinib, n = 179; chlorambucil-obinutuzumab, n = 177). Median age was 70 years, 63.0% had unmutated immunoglobulin heavy chain variable region gene (uIGHV), 13.6% had del(17p) and/or mutated TP53, and 17% had complex karyotype (CK; ≥3 chromosomal abnormalities). Median progression-free survival (PFS) was not reached (NR) for acalabrutinib-obinutuzumab and acalabrutinib vs 27.8 months for chlorambucil-obinutuzumab (both P < .0001); estimated 72-month overall PFS rates were 78.0%, 61.5%, and 17.2%, respectively. Acalabrutinib-obinutuzumab resulted in improved PFS vs acalabrutinib monotherapy (hazard ratio [HR], 0.58; P = .0229). Patients with uIGHV, del(17p) and/or mutated TP53, or CK had significantly improved PFS with acalabrutinib ± obinutuzumab vs chlorambucil-obinutuzumab (P < .0001, P ≤ .0009, and P < .0001 for both acalabrutinib-containing arms, respectively). Median overall survival (OS) was NR for all treatments, with significantly longer OS for acalabrutinib-obinutuzumab than chlorambucil-obinutuzumab (HR, 0.62; P = .0349). Estimated 72-month OS rates were 83.9%, 75.5%, and 74.7% for acalabrutinib-obinutuzumab, acalabrutinib, and chlorambucil-obinutuzumab, respectively. Adverse events (AEs) occurring after >4 years were mostly grade 1 to 2. Rates of AEs, serious AEs, and events of clinical interest were similar between acalabrutinib-containing arms and consistent with the known safety profiles of acalabrutinib and obinutuzumab. Efficacy and safety of acalabrutinib-containing arms were maintained, with longer PFS in both acalabrutinib arms than chlorambucil-obinutuzumab including in patients with high-risk features. This trial was registered at www.ClinicalTrials.gov as #NCT02475681.

Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN / Sharman, J. P.; Egyed, M.; Jurczak, W.; Skarbnik, A.; Patel, K.; Flinn, I. W.; Kamdar, M.; Munir, T.; Walewska, R.; Hughes, M.; Fogliatto, L. M.; Herishanu, Y.; Banerji, V.; Follows, G.; Walker, P.; Ghia, P.; Janssens, A.; Byrd, J. C.; Ferrant, E.; Ferrajoli, A.; Wierda, W. G.; Wachira, C. W.; Suterwala, B. T.; Miranda, P.; Munugalavadla, V.; Wun, C. -C.; Woyach, J. A.. - In: BLOOD. - ISSN 0006-4971. - 146:11(2025), pp. 1276-1285. [10.1182/blood.2024024476]