SAN DIEGO In higher-risk patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who fail hypomethylating agent treatment, no induction strategy is superior to another with respect to outcomes and safety, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.1

“Hypomethylating agents like azacitidine and decitabine are common treatment for AML and MDS,” said Brian Ball, MD, a hematologist at Yale-New Haven Hospital in Connecticut. “Hypomethylating agent failure inevitably occurs, with primary failure occurring in at least 60% of patients and secondary failure eventually occurring in almost all responders to a hypomethylating agent.”

Investigators evaluated outcomes in patients with MDS and AML treated with different induction chemotherapy regimens after hypomethylating agent failure and identified risk factors associated with survival and response.

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Researchers analyzed data from 366 patients higher-risk AML or MDS who failed to respond or experienced progression after at least 1 cycle of a hypomethylating agent and were treated with intensive chemotherapy thereafter.

Of those, 203 received salvage induction with 7+3 chemotherapy with cytarabine and an anthracycline, 56 received intermediate to high-dose cytarabine (IDAC), and 107 received a nucleoside analogue (NA)-based regimen (fludarabine, cladribine, clofarabine).

“Even after hypomethylating agent failure, induction chemotherapy may lead to responses in 40% of patients,” said Dr Ball. “Choice of induction regimen has a limited impact on response and survival. Long-term survival was achieved only in the allogeneic transplantation group.”

Median overall survival for the entire cohort was 10.1 months. For 7+3, NA-based regimens, and IDAC, median overall survival was 9.2 months, 12.6 months, and 10.7 months, respectively.

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“Chemotherapy after hypomethylating agent failure is a reasonable option, especially for younger patients aged less than 70 years and those with non-adverse cytogenetics,” Dr Ball concluded. “Study limitations include the unavailability of geno-molecular profiling and retrospective design.”


  1. Ball B, Komrokji RS, Ades L, et al. Evaluation of salvage induction chemotherapy regimens in higher risk myelodysplastic syndrome and acute myeloid leukemia after hypomethylating agent treatment failure. Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.