Acalabrutinib treatment for older (aged ≥80 years) and/or frail patients with CLL: primary end point analysis of the CLL-Frail trial
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.
Article Details
Authors (32)
Florian Simon
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany
Rudy Ligtvoet
1Department I of Internal Medicine and Center of Integrated Oncology Aachen, Bonn, Cologne, Düsseldorf, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
Jan-Paul Bohn
Medical University of Innsbruck, Department of Hematology and Oncology, Innsbruck, Austria
Thomas Nösslinger
173rd Medical Department for Hematology and Oncology, Hanusch Krankenhaus, Vienna, Austria
Julia von Tresckow
4Department of Hematology, Oncology and Palliative Care, Katholisches Klinikum Bochum, Ruhr University Bochum, Bochum, Germany
Rüdiger Liersch
5Gemeinschaftspraxis für Hämatologie und Onkologie, Clemenshospital Münster, Münster, Germany
Tobias Gaska
Bruederkrankenhaus Paderborn, Paderborn, Germany
Kathleen Jentsch-Ullrich
7Gemeinschaftspraxis für Hämatologie und Onkologie, Magdeburg, Germany
Michael Gärtner
8Onkologisches Ambulanzzentrum Hannover, Hannover, Germany
Thomas Wolff
9OncoResearch Lerchenfeld, Hamburg, Germany
Ingo Schwaner
10Onkologische Schwerpunktpraxis Kurfürstendamm, Berlin, Germany
Dominik Wolf
Christof Schneider
Division of CLL, Department of Internal Medicine III, Ulm University, Ulm, Germany
Ursula Vehling-Kaiser
Day Clinic Hematology Oncology Palliative Care
Matthias Ritgen
Universitaetsklinikum Schleswig-Holstein, Medizinische Klinik II, Kiel, Germany
Christian Spoer
14MVZ Klinikum Deggendorf, Deggendorf, Germany
Michael Eckart
15Practice for Oncology and Hematology, Erlangen, Germany
Thomas Decker
16Oncological Practice, Ravensburg, Germany
Geothy Chakupurakal
17Praxis für Hämatologie und Onkologie, Koblenz, Germany
Björn Schöttker
32Hämatologisch-Onkologische Schwerpunktpraxis Würzburg, Würzburg, Germany
Jens Kisro
19Lübecker Onkologische Schwerpunktpraxis, Lübeck, Germany
Karl-Anton Kreuzer
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany
Eugen Tausch
Division of CLL, Department of Internal Medicine III, Ulm University, Ulm, Germany
Stephan Stilgenbauer
Division of CLL, Department of Internal Medicine III, Ulm University, Ulm, Germany
Sandra Robrecht
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany
Janina Stumpf
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany
Anna-Maria Fink
University Hospital of Cologne, Cologne, Germany
Moritz Fürstenau
1Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German CLL Study Group, University of Cologne, Cologne, Germany
Kirsten Fischer
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany
Valentin Goede
20Department of Oncogeriatrics, St Marien Hospital, Cologne, Germany
Michael Hallek
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany
Barbara Eichhorst
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany