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.

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Publication Details

Journal
Blood
Published
2025-09-04
DOI
https://doi.org/10.1182/blood.2025028550
Citations
6
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
9.75

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article

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

Stephan Stilgenbauer, Florian Simon, Christian Spoer, Rudy Ligtvoet et al.
6 citations
Blood
Chronic Lymphocytic Leukemia Research
9.75
article

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

Stephan Stilgenbauer, Florian Simon, Christian Spoer, Rudy Ligtvoet, Julia von Tresckow, Ingo Schwaner, Thomas Decker, Dominik Georg Friedrich Wolf, Miriam Gärtner, Jan‐Paul Bohn, Eugen Tausch, Ursula Vehling‐Kaiser, Geothy Chakupurakal, Thomas Nösslinger, Thomas Wolff, Björn Schöttker, Moritz Fürstenau, Kirsten Fischer, Jens Kisro, Sandra Robrecht, Kathleen Jentsch‐Ullrich, Rüdiger Liersch, Anna Maria Fink, Michael J. Eckart, Matthias Ritgen, Michael J. Hallek, Janina Stumpf, Christof Schneider, Barbara F. Eichhorst, Valentin Goede, Karl‐Anton Kreuzer, Tobias Gaska
article en
6 citations

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.

BloodVol. 146(26)
Innsbruck Medical University (AT), Koblenz University of Applied Sciences (DE), University of Cologne (DE), Universität Innsbruck (AT), Universität Ulm (DE), University of Applied Sciences Landshut (DE), Hochschule für Angewandte Wissenschaften Kiel (DE), Christian-Albrechts-Universität zu Kiel (DE), Universitätsklinikum Erlangen (DE), Düsseldorf University Hospital (DE), Integrated Oncology (United States) (US), Ravensburg University of Cooperative Education (DE), Hanusch Hospital (AT), University Hospital Schleswig-Holstein (DE), St. Marien Hospital (DE), Universitätsklinikum Würzburg (DE), Brüderkrankenhaus St. Josef Paderborn (DE), Clemenshospital Münster (DE), Praxis für Humangenetik (DE), Praxis für Hämatologie und Onkologie (DE), MVZ - Kurfürstendamm (DE), Procon (Germany) (DE), Institut für Versorgungsforschung in der Onkologie (DE), University Hospital Cologne (DE), Heinrich Heine University Düsseldorf (DE), University of Duisburg-Essen (DE), Deggendorf Institute of Technology (DE), University of Lübeck (DE)
Amgen, Eli Lilly and Company, AstraZeneca, GlaxoSmithKline, Gilead Sciences, Celgene, F. Hoffmann-La Roche, BeiGene, Deutsche Forschungsgemeinschaft
Openalex Percentile: Top 2%
Chronic Lymphocytic Leukemia Research
9.75
DOIOpen Access PDFOpenAlex
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