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

Author(s): Simon, Florian1; Ligtvoet, Rudy1; Bohn, Jan-Paul2; Nösslinger, Thomas3; von Tresckow, Julia4; Liersch, Rüdiger5; Gaska, Tobias6; Jentsch-Ullrich, Kathleen7; Gärtner, Michael8; Wolff, Thomas9; Schwaner, Ingo10; Wolf, Dominik2; Schneider, Christof11; Vehling-Kaiser, Ursula12; Ritgen, Matthias13; Spoer, Christian14; Eckart, Michael15; Decker, Thomas16; Chakupurakal, Geothy17; Schöttker, Björn18; Kisro, Jens19; Kreuzer, Karl-Anton1; Tausch, Eugen11; Stilgenbauer, Stephan11; Robrecht, Sandra1; Stumpf, Janina1; Fink, Anna-Maria1; Fürstenau, Moritz1; Fischer, Kirsten1; Goede, Valentin20; Hallek, Michael1; Eichhorst, Barbara1;
Source: Blood (2025) 146 (26): 3153–3162.
Original Article
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Acalabrutinib in patients aged ≥80 years demonstrated 12-month progression-free (PFS) and overall survival (OS) rates of 93.3% and 95.7%, respectively, after a median follow-up of 19 months. Adverse events were severe but rarely included major bleeding or atrial fibrillation. Patient-reported quality of life improved, including amerlioration of frailty.

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.

Author Affiliations

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; 2Department of Internal Medicine V–Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria; 3Third Medical Department for Hematology and Oncology, Hanusch Krankenhaus Wien, Vienna, Austria; 4Clinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; 5Gemeinschaftspraxis für Hämatologie und Onkologie, Clemenshospital Münster, Münster, Germany; 6Brüderkrankenhaus St. Josef Paderborn, Klinik für Hämatologie und Onkologie, Paderborn, Germany; 7Gemeinschaftspraxis für Hämatologie und Onkologie, Magdeburg, Germany; 8Onkologisches Ambulanzzentrum Hannover, Hannover, Germany; 9OncoResearch Lerchenfeld, Hamburg, Germany; 10Onkologische Schwerpunktpraxis Kurfürstendamm, Berlin, Germany; 11Department of Internal Medicine III, Sektion CLL, Ulm University, Ulm, Germany; 12Outpatient Clinic, Landshut, Germany; 13Department II of Internal Medicine, University of Schleswig-Holstein, Kiel, Germany; 14MVZ Klinikum Deggendorf, Deggendorf, Germany; 15Practice for Oncology and Hematology, Erlangen, Germany; 16Oncological Practice, Ravensburg, Germany; 17Praxis für Hämatologie und Onkologie, Koblenz, Germany; 18Practice for Oncology and Hematology, Würzburg, Germany; 19Lübecker Onkologische Schwerpunktpraxis, Lübeck, Germany; 20Department of Oncogeriatrics, St Marien Hospital, Cologne, Germany

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