Acalabrutinib treatment for older (aged ≥80 years) and/or frail patients with CLL: primary end point analysis of the CLL-Frail trial
Florian Simon, Rudy Ligtvoet, Jan‐Paul Bohn, Thomas Nösslinger, Julia von Tresckow, Rüdiger Liersch, Tobias Gaska, Kathleen Jentsch‐Ullrich, Miriam Gärtner, Thomas Wolff, Ingo Schwaner, Dominik Wolf, Christof Schneider, Ursula Vehling‐Kaiser, Matthias Ritgen, Christian Spoer, Michael J. Eckart, Thomas Decker, Geothy Chakupurakal, Björn Schöttker, Jens Kisro, Karl‐Anton Kreuzer, Eugen Tausch, Stephan Stilgenbauer, Sandra Robrecht, Janina Stumpf, Anna Maria Fink, Moritz Fürstenau, Kirsten Fischer, Valentin Goede, Michael Hallek, Barbara Eichhorst
Abstract
ABSTRACT: 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.