Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial.
RESPONSE is an open-label phase 3 study evaluating the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib versus best available therapy for efficacy/safety in hydroxyurea-resistant or intolerant patients with polycythemia vera. This preplanned analysis occurred when all patients completed the Week 80 visit or discontinued. Objectives included evaluating the durability of the primary response (Week 32 phlebotomy-independent hematocrit control plus ≥35% spleen volume reduction), its components, and that of complete hematologic remission; and long-term safety. Median exposure was 111 weeks; 91/110 (82.7%) patients randomized to ruxolitinib remained on treatment. No patients continued best available therapy (98/112 [87.5%] crossed over to ruxolitinib, most at/soon after Week 32). At Week 32, primary response was achieved by 22.7% vs. 0.9% of patients randomized to ruxolitinib and best available therapy, respectively (hematocrit control, 60.0% vs. 18.8%; spleen response, 40.0% vs. 0.9%). The probability of maintaining primary and hematocrit responses for ≥80 weeks was 92% and 89%, respectively; 43/44 spleen responses were maintained until Week 80. Complete hematologic remission at Week 32 was achieved in 23.6% of ruxolitinib-randomized patients; the probability of maintaining complete hematologic remission for ≥80 weeks was 69%. Among ruxolitinib crossover patients, 79.2% were not phlebotomized, and 18.8% achieved a ≥35% reduction from baseline in spleen volume after 32 weeks of treatment. New or worsening hematologic laboratory abnormalities in ruxolitinib-treated patients were primarily grade 1/2 decreases in hemoglobin, lymphocytes, and platelets. The thromboembolic event rate per 100 patient-years was 1.8 with randomized ruxolitinib treatment vs. 8.2 with best available therapy. These data support ruxolitinib as an effective long-term treatment option for hydroxyurea-resistant or intolerant patients with polycythemia vera. This trial was registered at clinicaltrials.gov identifier: 01243944.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA sverstov@mdanderson.org.
Srdan
S
Verstovsek
Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Italy.
Alessandro M
AM
Vannucchi
Johannes Wesling Clinic, Minden, Germany.
Martin
M
Griesshammer
St. István and St. László Hospital, Semmelweis University 3 Department of Internal Medicine, Budapest, Hungary.
Tamas
T
Masszi
Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.
Simon
S
Durrant
Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
Francesco
F
Passamonti
Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Claire N
CN
Harrison
University of Naples Federico II, Italy.
Fabrizio
F
Pane
ZNA Stuivenberg, Antwerp, Belgium.
Pierre
P
Zachee
Department of Hematology and Oncology, University of Yamanshi, Chuo-shi, Japan.
Keita
K
Kirito
Hematology Department, Hospital del Mar, Barcelona, Spain.
Carlos
C
Besses
Department of Clinical Hematology and Diagnostics, Osaka City University Graduate School of Medicine, Japan.
Masayuki
M
Hino
Hospital Jose Maria Ramos Mejia, Buenos Aires, Argentina.
Beatriz
B
Moiraghi
Saint Agnes Cancer Institute, Baltimore, MD, USA.
Carole B
CB
Miller
Department of Hematology, University of Pavia, Italy.
Mario
M
Cazzola
Center for the Study of Myelofibrosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
Vittorio
V
Rosti
Medical Department, Division of Hematology, Oncology, and Tumor Immunology, Charité Universitätsmedizin Berlin, Germany.
Igor
I
Blau
Department of Hematology/Oncology, Mayo Clinic Cancer Center, Scottsdale, AZ, USA.
Ruben
R
Mesa
Incyte Corporation, Wilmington, DE, USA.
Mark M
MM
Jones
Incyte Corporation, Wilmington, DE, USA.
Huiling
H
Zhen
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Jingjin
J
Li
Novartis Pharma S.A.S, Rueil Malmaison, France.
Nathalie
N
Francillard
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Dany
D
Habr
Centre d'Investigations Cliniques (INSERM CIC 1427), Hôpital Saint-Louis and Université Paris Diderot, Paris, France.
Jean-Jacques
JJ
Kiladjian
D000328:Adult; D000368:Aged; D000483:Alleles; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D006400:Hematocrit; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009570:Nitriles; D011087:Polycythemia Vera / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D016896:Treatment Outcome
D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases