Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the RuxoBEAT clinical trial of the GSG-MPN study group

Annals of Hematology - Tập 102 - Trang 349-358 - 2022
Steffen Koschmieder1,2, Susanne Isfort1,2, Dominik Wolf2,3,4, Florian H. Heidel5,6, Andreas Hochhaus5, Philippe Schafhausen7, Martin Griesshammer8, Denise Wolleschak9, Uwe Platzbecker10,11, Konstanze Döhner12, Philipp J. Jost13,14, Stefani Parmentier15,16, Markus Schaich15, Nikolas von Bubnoff17,18, Frank Stegelmann12, Angela Maurer1,2, Martina Crysandt1,2, Deniz Gezer1,2, Maike Kortmann2,19, Jeremy Franklin2,20, Julia Frank2,20, Martin Hellmich2,20, Tim H. Brümmendorf1,2
1Department of Medicine (Hematology, Oncology, Hemostaseology, and SCT), Faculty of Medicine, RWTH Aachen University, Aachen, Germany
2Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany
3Internal Medicine 3, Oncology, Hematology and Rheumatology, University Clinic Bonn (UKB), Bonn, Germany
4Internal Medicine V, Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria
5Hematology and Oncology, Jena University Hospital, Jena, Germany
6Internal Medicine C, Greifswald University Medicine, Greifswald, Germany
7Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
8Department of Hematology/Oncology, Klinikum Minden, Germany
9Department of Hematology/Oncology, Otto-Von-Guericke University Medical Center Magdeburg, Magdeburg, Germany
10Department of Internal Medicine 1, University of Dresden, Dresden, Germany
11Department of Medicine I – Hematology, Cell Therapy, Hemostaseology, University of Leipzig, Leipzig, Germany
12Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
13Medical Department III, Hematology and Oncology, and Center for Translational Cancer Research, Translatum, Technical University of Munich, Munich, Germany
14Division of Clinical Oncology, Internal Medicine, Medical University of Graz, Graz, Austria
15Department of Hematology, Oncology and Palliative Medicine, Rems-Murr Klinikum, Winnenden, Germany
16Oncology and Hematology, Tumor Center, St. Claraspital, Basel, Switzerland
17Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine, Freiburg, Freiburg, Germany and German Cancer Consortium (DKTK), Freiburg, Germany
18Department of Hematology and Oncology, Medical Center, University of Schleswig-Holstein, Lübeck, Germany
19Center for Translational & Clinical Research (CTC-A), Faculty of Medicine, RWTH Aachen University, Aachen, Germany
20Institute of Medical Statistics and Computational Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

Tóm tắt

Patients (pts) with polycythemia vera (PV) suffer from pruritus, night sweats, and other symptoms, as well as from thromboembolic complications and progression to post-PV myelofibrosis. Ruxolitinib (RUX) is approved for second-line therapy in high-risk PV pts with hydroxyurea intolerance or resistance. The RuxoBEAT trial (NCT02577926, registered on October 1, 2015, at clinicaltrials.gov) is a multicenter, open-label, two-arm phase-IIb trial with a target population of 380 pts with PV or ET, randomized to receive RUX or best available therapy. This pre-specified futility analysis assesses the early clinical benefit and tolerability of RUX in previously untreated PV pts (6-week cytoreduction was allowed). Twenty-eight patients were randomly assigned to receive RUX. Compared to baseline, after 6 months of treatment, there was a significant reduction of median hematocrit (46 to 41%), the median number of phlebotomies per year (4.0 to 0), and median patient-reported pruritus scores (2 to 1), and a trend for reduced night sweat scores (1.5 to 0). JAK2V617F allele burden, as part of the scientific research program, also significantly decreased. One hundred nine adverse events (AEs) occurred in 24/28 patients (all grade 1 to 3), and no pt permanently discontinued treatment because of AEs. Thus, treatment with ruxolitinib in untreated PV pts is feasible, well-tolerated, and efficient regarding the above-mentioned endpoints.

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Annals of Hematology

Tập 102

349-358

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