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Acalabrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKi), offers an improved safety profile compared to first-generation inhibitors like ibrutinib. While BTKi guidelines exist, practical differences between BTKis-such as drug interactions and tolerance-are not fully addressed. Therefore, a consensus on acalabrutinib use would benefit the medical community. This 2-round Delphi study involved hematologists, pharmacists, cardiologists, dermatologists, and nurse practitioners throughout France to establish consensus-based practical guidance on managing adverse events (AEs) associated with acalabrutinib in chronic lymphocytic leukemia. Key findings highlighted the need for a hospital pharmacist to analyze drug interactions before starting acalabrutinib. Additionally, the experts' opinion was to avoid the concomitant use of acalabrutinib with strong CYP3A inhibitors due to an increased risk of toxicity and with strong CYP3A inducers due to potential efficacy concerns. Importantly, our study did not find contraindications for acalabrutinib in patients with current or previous atrial fibrillation. The panel emphasized the importance of measuring blood pressure at every clinical visit for patients treated with acalabrutinib and opposed the initiation of acalabrutinib in patients on both aspirin and clopidogrel. For invasive dermatological or dental procedures, acalabrutinib should be discontinued 4 days prior and resumed 48 hours postprocedure in the absence of bleeding. Additionally, patients should be informed about the risk of headaches, particularly during the first month of treatment, and paracetamol use in combination with caffeine is recommended for managing grade ≥ 2 headaches under acalabrutinib treatment. This Delphi study underscored the effectiveness of a collaborative process in enhancing the management of acalabrutinib-associated AEs., Competing Interests: Disclosure LY received consulting fees from AbbVie, AstraZeneca, BeiGene, BMS/Celgene, Gilead/Kite, Janssen, and Roche. SE received consultancy fees from Amgen, AstraZeneca, Bayer, BMS, Eisai, Leo Pharma, and Pierre Fabre. VL received honoraria from AbbVie, AstraZeneca, and BeiGene. VS received consulting fees from Novartis, BMS, MSD, Pierre Fabre, AstraZeneca, Janssen, Bayer, and Immunocore. CT received consulting fees from AbbVie, AstraZeneca, Beigene, and Janssen. The other authors do not report any conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)