The impact of fitness and dose intensity on clinical outcomes with venetoclax-obinutuzumab in CLL
Abstract
Abstract Venetoclax-obinutuzumab (Ven-Obi) is a standard first-line therapy for chronic lymphocytic leukemia (CLL). The impact of age, fitness, and dose reductions remains unclear. We analyzed patients treated with Ven-Obi in the CLL13 and CLL14 trials, excluding patients with TP53 aberrations. Fitness was assessed using the cumulative illness rating scale (CIRS, >6) and creatinine clearance (≤70 mL/min). Among 410 patients (median age, 67 years), 55.7% were unfit (median age, 72 years) and 44.3% were fit (median age, 58 years). Overall response rate (ORR) was 89.5% in unfit and 96.1% in fit patients. Rates of undetectable minimal residual disease (uMRD) at <10–4 were 80.3% in unfit and 85.1% in fit patients. Progression-free survival (PFS) at 3 years was 86.4% vs 87.5% (hazard ratio, [HR], 1.12; 95% confidence interval [CI], 0.70-1.81; P = .63). Overall survival at 3 years was 91.8% vs 96.9% (HR, 2.02; 95% CI, 0.90-4.55; P = .088). Adverse events included neutropenia (62.7% unfit, 56.9% fit), infusion-related-reactions (44.3% unfit, 56.9% fit), fatigue (15.8% unfit, 35.9% fit), and infections (57.5% unfit, 69.6% fit). Venetoclax dose reductions of <80% occurred in 39.6% of unfit and 17.6% of fit patients, with lower ORR (83.3% vs 98.2%) and uMRD rates (74.2% vs 87.9%) in those with reduced dose intensities, but similar PFS. Dose reductions of <70% were associated with shorter PFS. Overall, this study shows comparable efficacy and toxicity of Ven-Obi in fit and unfit patients with CLL.
Article Details
Authors (34)
Othman Al-Sawaf
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
Adam Giza
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
Sandra Robrecht
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany
Julia von Tresckow
4Department of Hematology, Oncology and Palliative Care, Katholisches Klinikum Bochum, Ruhr University Bochum, Bochum, Germany
Anna-Maria Fink
University Hospital of Cologne, Cologne, Germany
Florian Simon
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
Christof Schneider
Division of CLL, Department of Internal Medicine III, Ulm University, Ulm, Germany
Liliya Sivcheva
4First Department of Internal Medicine, Hristo Botev Multiprofile Hospital for Active Treatment, Vratsa, Bulgaria
Anthony Schwarer
5Department of Haematology, Box Hill Hospital, Melbourne, Australia
Javier Loscertales
Hospital Universitario La Princesa, Madrid
Robert Weinkove
Dirk Strumberg
Allanah Kilfoyle
10Haematology Department, Palmerston North Hospital, Palmerston North, New Zealand
Gunnar Juliusson
Caspar da Cunha-Bang
Rigshospitalet, Copenhagen University Hospital, Copenhagen
Thomas Illmer
Berufsausüebungsgemeinschaft, Gokos, Dresden, Germany
Michael Gregor
Cantonal Hospital of Lucerne, Lucerne, Switzerland
Patrick Thornton
Cancer Clinical Trials and Research Unit, Cancer Trials Ireland, Beaumont Hospital, Dublin
Ann Janssens
Universitaire Ziekenhuizen Leuven, Leuven, Belgium
Tamar Tadmor
Bnai Zion Medical Center, Technion, Haifa, Israel
Vesa Lindström
Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki
Philipp Staber
19Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Mark-David Levin
Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands
Clemens-Martin Wendtner
Ludwig-Maximilians University (LMU), Medical Clinic III, Munich, Germany
Karl-Anton Kreuzer
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany
Matthias Ritgen
Universitaetsklinikum Schleswig-Holstein, Medizinische Klinik II, Kiel, Germany
Stephan Stilgenbauer
Division of CLL, Department of Internal Medicine III, Ulm University, Ulm, Germany
Arnon P. Kater
Amsterdam University Medical Center location University of Amsterdam, Department of Hematology
Carsten Niemann
24Department of Hematology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
Kirsten Fischer
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
Michael Hallek
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany