5 years ago

A Phase II Trial of Ruxolitinib in Combination with Azacytidine in Myelodysplastic Syndrome/Myeloproliferative Neoplasms

Lingsha Zhou, Keyur Patel, Juliana Hidalgo-Lopez, Xuemei Wang, Prithviraj Bose, Zeev Estrov, Sherry Pierce, Guillermo Garcia-Manero, Srdan Verstovsek, Gautam Borthakur, Courtney D. Dinardo, Elias Jabbour, Graciela Nogueras-Gonzalez, Naval Daver, Rajyalakshmi Luthra, Naveen Pemmaraju, Carlos Bueso-Ramos, Jorge E. Cortes, Romany Gergis, Carla Tuttle, Rita Assi, Tapan Kadia, Hagop M. Kantarjian
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/m2 (Day 1-5) intravenously or subcutaneously was recommended to be added to each cycle starting cycle 4 and could be increased to 75 mg/m2 (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 = 0.02) and had splenomegaly (P = 0.03) compared to non-responders. 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 = 0.034). 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. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/ajh.24972

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