Acalabrutinib treatment for older (aged ≥80 years) and/or frail patients with CLL: primary end point analysis of the CLL-Frail trial.

Because frail patients and patients aged ≥80 years with chronic lymphocytic leukemia (CLL) are still underrepresented in clinical trials, the CLL-Frail trial aimed to evaluate the efficacy and safety of acalabrutinib in these patients. The primary end point was the overall response rate (ORR) after 6 cycles of treatment to test the null hypothesis of ORR ≤65%. Fifty-three patients were included in the trial, and 34 patients are still on therapy. Adverse events (AEs) were the most frequent reason for early discontinuation (10 patients), whereas 5 patients stopped treatment because of death. Median age was 81 years, and 47.2% of patients were frail. The ORR for the 46 patients receiving ≥3 cycles of treatment was 93.5% (95% confidence interval, 82.1-98.6) meeting the primary end point of this trial (P < .001). The estimated 12-month progression-free and overall survival rates were 93.3% and 95.7%, respectively, after a median follow-up of 19 months. 53.5% of patients reported an improvement in their self-perceived frailty. Although all patients experienced AEs, and severe (Common Terminology Criteria of ≥3) events were reported in 63.5% of patients, there were no events of severe bleeding and atrial fibrillation was rare (2 cases of Common Terminology Criteria Grades 2 and 3). Five patients died, of which 4 deaths happened during or <28 days after treatment. Infections/COVID-19 were the cause of death in 3 cases. To our knowledge, this is the first prospective trial in older and/or frail patients with CLL demonstrating a high efficacy and safe treatment with acalabrutinib monotherapy. This trial was registered at www.ClinicalTrials.gov as #NCT04883749.