A MATCHING‐ADJUSTED INDIRECT COMPARISON OF THE EFFICACY AND SAFETY OF ACALABRUTINIB VERSUS ZANUBRUTINIB IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA

Introduction: Next-generation Bruton tyrosine kinase inhibitors (BTKis) acalabrutinib (acala) and zanubrutinib (zanu) were compared with the standard of care BTKi ibrutinib in relapsed/refractory chronic lymphocytic leukemia (RR CLL) head-to-head randomized clinical trials (RCTs) ELEVATE-RR ALPINE, respectively. However, differences these RCT’s populations prevent comparison acala zanu. ASCEND, another RCT assessing acala, had a similar population to ALPINE but different comparator. Thus, we used unanchored matching-adjusted indirect (MAIC) compare efficacy safety vs zanu using individual patient data (IPD) from ASCEND published aggregate ALPINE. Methods: Acala IPD weighted match baseline This reduced variables that prognostic/effect-modifying progression-free survival (PFS) an exploratory multivariate cox regression analysis ASCEND. These included sex, ECOG PS, bulky disease, prior chemoimmunotherapy, del(11q), del(17p), TP53 without IGHV status, region, age, lines therapy Rai stage. An assessed investigator-assessed PFS (INV PFS) patients (acala, n = 149; zanu, 327). Pseudo for INV obtained Kaplan-Meier curves. A odds ratios (ORs) adverse events (AEs) treated 148; 324). To incidence AEs, artificial cut-off (Feb 21, 2020) was imposed median treatment exposure (both 28.4 months). Results: After matching, effective sample size 99 (66.6%; 65% male; age 66 years). 12- 24-month are shown Table 1. The MAIC hazard ratio (HR) is zanu: HR 0.90, 95% confidence interval (CI) 0.60–1.36. risk having grade ≥3 AE (OR 0.66, CI 0.41–1.05), atrial fibrillation (AF; OR 1.32, 0.56–3.08), AF/atrial flutter 0.60, 0.12–2.89), hemorrhage 0.61, 0.19–2.03) or leading discontinuation 1.14, 0.61–2.13) serious 0.39–0.97), hypertension (any grade: 0.18, 0.09–0.37; ≥3: 0.22, 0.09–0.54), any 0.54, 0.34–0.87) dose reduction 0.30, 0.14–0.67) favored Conclusions: have RR CLL, while has lower hemorrhage, due AEs Limitations MAICs mean results should be viewed as hypothesis-generating. Encore Abstract—previously submitted ASCO 2023, EHA 2023 research funded by: AstraZeneca Keyword: Chronic Lymphocytic Leukemia (CLL) Conflicts interests pertinent abstract P. Ghia Consultant advisory role AbbVie, AstraZeneca, BeiGene, BMS, Janssen, Lilly/Loxo Oncology, MSD, Roche Honoraria: Research funding: A. Skarbnik Abbvie, Genentech, Genmab, Novartis, Kite Pharma, Epizyme, Morphosys, Pharmacyclcics, SeaGen, TG Therapeutics, Lilly (LOXO) Other remuneration: Speakers' Bureau: Beigene, Celgene, Pharmacyclics, Therapeutics M. Miranda Employment leadership position: Stock ownership: S. Yong J. Roos Patient/Royalties/Other Intellectual Property: CalciMedica R. Hettle Palazuelos-Munoz V. Shetty Verona Pharma Kittai Eli Lilly, KITE Speaker's bureau: Beigene