Hypomethylating agents in relapsed and refractory AML: Outcomes and their predictors in a large international patient cohort

Maximilian Stahl, Michelle DeVeaux, Pau Montesinos, Raphael Itzykson, Ellen K. Ritchie, Mikkael A. Sekeres, John D. Barnard, Nikolai A. Podoltsev, Andrew M. Brunner, Rami S. Komrokji, Vijaya R. Bhatt, Aref Al-Kali, Thomas Cluzeau, Valeria Santini, Amir T. Fathi, Gail J. Roboz, Pierre Fenaux, Mark R. Litzow, Sarah Perreault, Tae Kon KimThomas Prebet, Norbert Vey, Vivek Verma, Ulrich Germing, Juan Miguel Bergua, Josefina Serrano, Steven D. Gore, Amer M. Zeidan

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.

Original languageEnglish (US)
Pages (from-to)923-932
Number of pages10
JournalBlood Advances
Issue number8
StatePublished - Apr 24 2018

ASJC Scopus subject areas

  • Hematology


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