The American Society of Clinical Oncology (ASCO) promotes the routine use of a comprehensive geriatric assessment, particularly emphasizing frailty, to identify vulnerabilities not detected in the standard clinical evaluation. However, frailty remains an under-explored topic in Chronic Lymphocytic Leukemia (CLL), especially concerning modern treatments such as Bruton's tyrosine kinase inhibitors (BTKi). There's a paucity of data linking this assessment to treatment toxicity. Objective: To document the clinical progression of CLL patients undergoing Acalabrutinib treatment and correlate toxicity with a frailty assessment protocol. Methodology: Patients treated with Acalabrutinib underwent a specific geriatric assessment protocol. For frailty assessment, the modified Fried frailty criteria and the Frail Scale were employed. The Lawton scale was used to gauge functionality in instrumental activities of daily living (IADL), and sarcopenia was assessed in accordance with the updated guidelines from the European Working Group on Sarcopenia.

Two patients were clinically categorized as frail and one as robust. Patient J.R.M, a 95-year-old female without significant comorbidities, was classified as frail, sarcopenic, and dependent for IADLs. She commenced treatment with Acalabrutinib, but after nine days, experienced severe skin bleeding leading to drug discontinuation. The second patient, M.N.G.O, a 78-year-old hypertensive female, was also identified as frail, sarcopenic, with IADL impairment. After initiating Acalabrutinib therapy, she developed skin and muscular bleeding shortly after, prompting immediate cessation. The last patient, R.S.M, a 91-year-old male with well-managed multiple comorbidities, was categorized as robust and non-sarcopenic. He has been on Acalabrutinib treatment for CLL for 1 year and 7 months, displaying a positive therapeutic response, no side effects, and full independence in IADLs. Discussion: Acalabrutinib is a second generation BTKi, safer than Ibrutinib. Its use has been suggested as safe in any age group. Still, data in frail patients is scarce. The German CLL study group provided safety data on Acalabrutinib in elderly patients but did not specifically detail the adverse effects in patients meeting the criteria for frailty syndrome. Conclusion: The presented cases suggest that geriatric assessment may be a more accurate predictor of adverse events in BTKi treatment than chronological age. Thiago Xavier Carneiro receives honoraria from Janssen.