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CLL-1304: Comparative Safety of Ibrutinib vs Acalabrutinib in Chronic Lymphocytic Leukemia: A Propensity-Score-Matched Analysis of Real-World Outcomes
Abstract   Peer reviewed

CLL-1304: Comparative Safety of Ibrutinib vs Acalabrutinib in Chronic Lymphocytic Leukemia: A Propensity-Score-Matched Analysis of Real-World Outcomes

Ali Mohsin, Faiza Khan, Muhammad Furqan, Hafiz Muhammad Majid Ilyas, Hasan Ilyas, Muhammad Tayyab Tahir, Muhammad Usman Haider, Ishtiaq Ahmad, Javeria Benyamin and Sana Asif
Clinical lymphoma, myeloma and leukemia, Vol.26(Suppl 1), pp.S640-S640
08/2026
DOI: 10.1016/S2152-2650(26)02101-4

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Abstract

Background: Ibrutinib and acalabrutinib are approved Bruton’s tyrosine kinase (BTK) inhibitors for chronic lymphocytic leukemia (CLL), but real-world safety comparisons remain scarce. We evaluated the risk of bleeding, infection, atrial fibrillation (AFib), and hypertension (HTN) between these therapies. Methods: Using the TriNetX Global Collaborative Network, we identified adult CLL patients (ICD-10 C91.10/C91.12, excluding those with diffuse large B-cell lymphoma and Richter’s transformation) who initiated ibrutinib (n = 6945) or acalabrutinib (n = 4544). Propensity score matching (PSM) on age, sex, race, comorbidities, prior chemotherapy lines, and cardiovascular medication use yielded balanced cohorts of approximately 4349 pairs. Bleeding, respiratory and systemic infections, AFib/flutter, and HTN were assessed at 1, 3, 6, and 12 months with risk analysis and Kaplan-Meier methods. Results: After PSM, ibrutinib was associated with significantly higher infection risk from 1 month (9.6% vs 7.6%; hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.09–1.45; P = 0.002) through 12 months (30.4% vs 25.5%; HR, 1.14; 95% CI, 1.04–1.25; P = 0.006). Bleeding risk was numerically higher with ibrutinib at all time points; this effect reached significance from 3 months onward (HR, 1.42; 95% CI, 1.06–1.91; P = 0.018) and persisted at 12 months (5.5% vs 3.5%; HR, 1.48; 95% CI, 1.17–1.89; P = 0.001). Ibrutinib was associated with lower early risk of AFib at 1 month (6.3% vs 7.7%; HR, 0.80; 95% CI, 0.68–0.94; P = 0.008), but this effect reversed to significantly higher rates by 12 months (18.4% vs 15.4%; HR, 1.14; 95% CI, 1.03–1.26; P = 0.013). HTN was comparable at 1 month (HR, 1.02; P = 0.748) but significantly diverged from 3 months onward, with ibrutinib patients reaching higher 12-month rates (42.8% vs 36.8%; HR, 1.14; 95% CI, 1.07–1.22; P < 0.001). Conclusions: Acalabrutinib demonstrated a consistently more favorable safety profile across all four outcomes. These findings support acalabrutinib as the preferred BTK inhibitor for CLL, particularly for longer treatment durations.
 acalabrutinib atrial fibrillation CLL ibrutinib

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