Ruxolitinib and interferon-α2 combination therapy for patients with polycythemia vera or myelofibrosis: a phase II study
Anders Lindholm Sørensen,
Stine Ulrik Mikkelsen,
Trine Alma Knudsen,
Mads Emil Bjørn,
Christen Lykkegaard Andersen,
Ole Weis Bjerrum,
Nana Brochmann,
Dustin Andersen Patel,
Lise Mette Rahbek Gjerdrum,
Daniel El Fassi,
Torben A. Kruse,
Thomas Stauffer Larsen,
Hans Torben Mourits-Andersen,
Claus Henrik Nielsen,
Christina Ellervik,
Niels Pallisgaard,
Mads Thomassen,
Lasse Kjær,
Vibe Skov,
Hans Carl Hasselbalch
Affiliations
Anders Lindholm Sørensen
Department of Hematology, Zealand University Hospital, Roskilde, Denmark; Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
Stine Ulrik Mikkelsen
Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark
Trine Alma Knudsen
Department of Hematology, Zealand University Hospital, Roskilde, Denmark
Mads Emil Bjørn
Herlev University Hospital, Copenhagen, Denmark
Christen Lykkegaard Andersen
Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Public Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Ole Weis Bjerrum
Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
Nana Brochmann
Department of Hematology, Zealand University Hospital, Roskilde, Denmark
Dustin Andersen Patel
Department of Hematology, Zealand University Hospital, Roskilde, Denmark; Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
Lise Mette Rahbek Gjerdrum
Department of Pathology, Zealand University Hospital, Roskilde, Denmark
Daniel El Fassi
Herlev University Hospital, Copenhagen, Denmark
Torben A. Kruse
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
Thomas Stauffer Larsen
Department of Hematology, Odense University Hospital, Odense, Denmark
Hans Torben Mourits-Andersen
Department of Hematology, South-West Jutlandic Hospital, Esbjerg, Denmark
Claus Henrik Nielsen
Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
Christina Ellervik
Herlev University Hospital, Copenhagen, Denmark; Department of Laboratory Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA; Data and Development Support, Region Zealand, Sorø, Denmark
Niels Pallisgaard
Department of Pathology, Zealand University Hospital, Roskilde, Denmark
Mads Thomassen
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
Lasse Kjær
Department of Hematology, Zealand University Hospital, Roskilde, Denmark
Vibe Skov
Department of Hematology, Zealand University Hospital, Roskilde, Denmark
Hans Carl Hasselbalch
Department of Hematology, Zealand University Hospital, Roskilde, Denmark
We report the final 2-year end-of-study results from the first clinical trial investigating combination treatment with ruxolitinib and low-dose pegylated interferon-α2 (PEG-IFNα2). The study included 32 patients with polycythemia vera and 18 with primary or secondary myelofibrosis; 46 patients were previously intolerant of or refractory to PEGIFNα2. The primary outcome was efficacy, based on hematologic parameters, quality of life measurements, and JAK2 V617F allele burden. We used the 2013 European LeukemiaNet and International Working Group- Myeloproliferative Neoplasms Research and Treatment response criteria, including response in symptoms, splenomegaly, peripheral blood counts, and bone marrow. Of 32 patients with polycythemia vera, ten (31%) achieved a remission which was a complete remission in three (9%) cases. Of 18 patients with myelofibrosis, eight (44%) achieved a remission; five (28%) were complete remissions. The cumulative incidence of peripheral blood count remission was 0.85 and 0.75 for patients with polycythemia vera and myelofibrosis, respectively. The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score decreased from 22 [95% confidence interval (95% CI):, 16-29] at baseline to 15 (95% CI: 10-22) after 2 years. The median JAK2 V617F allele burden decreased from 47% (95% CI: 33-61%) to 12% (95% CI: 6-22%), and 41% of patients achieved a molecular response. The drop-out rate was 6% among patients with polycythemia vera and 32% among those with myelofibrosis. Of 36 patients previously intolerant of PEG-IFNα2, 31 (86%) completed the study, and 24 (67%) of these received PEG-IFNα2 throughout the study. In conclusion, combination treatment improved cell counts, reduced bone marrow cellularity and fibrosis, decreased JAK2 V617F burden, and reduced symptom burden with acceptable toxicity in several patients with polycythemia vera or myelofibrosis. #EudraCT2013-003295-12.
