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A phase II trial of ruxolitinib in combination with azacytidine in myelodysplastic syndrome/myeloproliferative neoplasms
Author(s) -
Assi Rita,
Kantarjian Hagop M.,
GarciaManero Guillermo,
Cortes Jorge E.,
Pemmaraju Naveen,
Wang Xuemei,
NoguerasGonzalez Graciela,
Jabbour Elias,
Bose Prithviraj,
Kadia Tapan,
Dinardo Courtney D.,
Patel Keyur,
BuesoRamos Carlos,
Zhou Lingsha,
Pierce Sherry,
Gergis Romany,
Tuttle Carla,
Borthakur Gautam,
Estrov Zeev,
Luthra Rajyalakshmi,
HidalgoLopez Juliana,
Verstovsek Srdan,
Daver Naval
Publication year - 2018
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24972
Subject(s) - ruxolitinib , medicine , discontinuation , myelodysplastic syndromes , anemia , international prognostic scoring system , myelofibrosis , gastroenterology , azacitidine , myeloproliferative neoplasm , thrombocytosis , bone marrow , platelet , biochemistry , gene expression , chemistry , dna methylation , gene
Ruxolitinib and azacytidine target distinct disease manifestations of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs). Patients with MDS/MPNs initially received ruxolitinib BID (doses based on platelets count), continuously in 28‐day cycles for the first 3 cycles. Azacytidine 25 mg/m 2 (Day 1‐5) intravenously or subcutaneously was recommended to be added to each cycle starting cycle 4 and could be increased to 75 mg/m 2 (Days 1‐5) for disease control. Azacytidine could be started earlier than cycle 4 and/or at higher dose in patients with rapidly proliferative disease or with elevated blasts. Thirty‐five patients were treated (MDS/MPN‐U, n =14; CMML, n =17; aCML, n =4), with a median follow‐up of 15.2 months (range, 1.0–41.5). All patients were evaluable by the 2015 international consortium proposal of response criteria for MDS/MPNs (ICP MDS/MPN) and 20 (57%) responded. Nine patients (45%) responded after the addition of azacytidine. A greater than 50% reduction in palpable splenomegaly at 24 weeks was noted in 9/14 (64%) patients. Responders more frequently were JAK2 ‐mutated ( P = .02) and had splenomegaly ( P = .03) compared to nonresponders. New onset grade 3/4 anemia and thrombocytopenia occurred in 18 (51%) and 19 (54%) patients, respectively, but required therapy discontinuation in only 1 (3%) patient. Patients with MDS/MPN‐U had better median survival compared to CMML and aCML (26.5 vs 15.1 vs 8 months; P = .034). The combination of ruxolitinib and azacytidine was well‐tolerated with an ICP MDS/MPN‐response rate of 57% in patients with MDS/MPNs. The survival benefit was most prominent in patients with MDS/MPN‐U.