Triple Combination Therapy for CLL: Acalabrutinib, Obinutuzumab and Chlorambucil

Patients with treatment-naive chronic lymphocytic leukemia (CLL) were randomized to receive either obinutuzumab (O) with acalabrutinib (A) or O plus chlorambucil (Clb) in the ELEVATE-TN (NCT02475681) trial. After a median of 5 years of follow-up, researchers want to share the ELEVATE-TN study’s most recent findings on efficacy and safety. After receiving informed consent, patients were randomly assigned to either the A+O, A, or O+Clb groups. Those who did not respond to O+Clb could switch to A monotherapy. Researchers examined PFS, ORR, OS, and safety as assessed by an independent review of case reports and patient records. Median age was 70 years old; 63% had unmutated IGHV and 9% had del(9q) among the 535 individuals studied (A+O, n=179; A, n=179; O+Clb, n=177) (17p). Median progression-free survival (PFS) was not reached (NR) for A+O (hazard ratio [HR]: 0.11) and A (HR]: 0.21) versus 27.8 months for O+Clb (both P0.0001) at a median follow-up of 58.2 months (range, 0.0-72.0; data cutoff Oct 1, 2021). The projected probabilities of survival at 60 months were 84% (A+O), 72% (A), and 21% (O+Clb).

Estimated 60-month PFS rates for the A+O, A, and O+Clb arms were 82%, 72%, and 6%, respectively, in patients with unmutated IGHV. The median PFS for the A+O and A-arms was not reached. Patients with del(17p) had an HR of 0.21 for those treated with A+O and A against 0.29 for those treated with A (P=0.0031 and P=0.0130, respectively); projected 60-month PFS rates of 75% (A+O), 71% (A), and 27% (O+Clb), respectively. Estimated 60-month OS rates for the A+O group were 90%, 84% for the A group, and 82% for the O+Clb group, with a median OS of NR in all therapy groups. Compared to O+Clb (83%; 77-88; P0.0001 [A+O], P=0.0499 [A]), the ORR was considerably greater with A+O (96%; 95% CI 92-98) and A (90%; 95% CI 85-94). A+O had a greater rate of complete response (CR) and CR with incomplete hematologic recovery (CRi) than O+Clb (13%/1%); 13%/1% had CR/CRi with A; the rate of CR has increased from the interim study (21% [A+O] and 7% [A]). The Table below details AEs and therapy administration. Sixty-five percent (A+O) and sixty percent (A) of patients are still receiving treatment, with adverse events (AEs) (17% [A+O], 16% [A], 14% [O+Clb]) and illness progression (6%) being the most common causes for treatment cessation. Seventy-two patients (41%) switched from O+Clb to A; however, 25% of them stopped taking it (10% owing to adverse events and 11% due to illness progression). Both A+O and A monotherapy were effective and safe after 5 years of follow-up, with A+O resulting in a considerably longer OS than O+Clb.

Source: https://library.ehaweb.org/eha/2022/eha2022-congress/357528/jeff.p.sharman.acalabrutinib.obinutuzumab.vs.obinutuzumab.2B.chlorambucil.in.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Aot_id%3D26848%2Amarker%3D1769%2Afeatured%3D17676

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02475681

Inc, M. G. (n.d.). ACALABRUTINIB ± OBINUTUZUMAB VS OBINUTUZUMAB + CHLORAMBUCIL IN… by Jeff P. Sharman. Library.ehaweb.org. Retrieved March 25, 2023, from https://library.ehaweb.org/eha/2022/eha2022-congress/357528/jeff.p.sharman.acalabrutinib.obinutuzumab.vs.obinutuzumab.2B.chlorambucil.in.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Aot_id%3D26848%2Amarker%3D1769%2Afeatured%3D17676