TY - JOUR
T1 - A phase II trial of ruxolitinib in combination with azacytidine in myelodysplastic syndrome/myeloproliferative neoplasms
AU - Assi, Rita
AU - Kantarjian, Hagop M.
AU - Garcia-Manero, Guillermo
AU - Cortes, Jorge E.
AU - Pemmaraju, Naveen
AU - Wang, Xuemei
AU - Nogueras-Gonzalez, Graciela
AU - Jabbour, Elias
AU - Bose, Prithviraj
AU - Kadia, Tapan
AU - Dinardo, Courtney D.
AU - Patel, Keyur
AU - Bueso-Ramos, Carlos
AU - Zhou, Lingsha
AU - Pierce, Sherry
AU - Gergis, Romany
AU - Tuttle, Carla
AU - Borthakur, Gautam
AU - Estrov, Zeev
AU - Luthra, Rajyalakshmi
AU - Hidalgo-Lopez, Juliana
AU - Verstovsek, Srdan
AU - Daver, Naval
N1 - Funding Information:
This study was funded by Incyte pharmaceuticals, the MD Anderson Cancer Center Support Grant CA016672, the MD Anderson Cancer Center Leukemia SPORE CA100632 from the National Cancer Institute, the Charif Souki Cancer Research Fund and philanthropic contributions to the MD Anderson Moon Shots Program. The funders had no role in data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Funding Information:
This study was supported by a grant from Incyte Inc. HK, GGM, JC, NP, SV, and ND have received research funding from Incyte. HK, GGM, JC, NP, EJ, PB, ZE, CBR, and ND have received honoraria from Incyte Inc.
Funding Information:
Incyte Pharmaceuticals and the MD Anderson Cancer Centre Leukaemia Support Grant (CCSG), Grant/Award Number: CA016672, the MD Anderson Cancer Center Leukemia, Grant/Award Number: SPORE CA100632, the Charif Souki Cancer Research Fund and generous philanthropic contributions to the MD Anderson Moon Shots Program
Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2018/2
Y1 - 2018/2
N2 - 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 =.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.
AB - 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 =.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.
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U2 - 10.1002/ajh.24972
DO - 10.1002/ajh.24972
M3 - Article
C2 - 29134664
AN - SCOPUS:85035104370
SN - 0361-8609
VL - 93
SP - 277
EP - 285
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 2
ER -