Hypomethylating agents super-responders: challenging the dogma of long-term remission for acute myeloid leukemia
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LETTER TO THE EDITOR
Hypomethylating agents super-responders: challenging the dogma of long-term remission for acute myeloid leukemia Joseph E. Maakaron 1 & Michael P. Ozga 2 & Gabriel N. Mannis 3 & Will Pulley 4 & Matthew C. Foster 4 & Joshua F. Zeidner 4 & Alice S. Mims 2 Received: 20 July 2019 / Accepted: 22 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Dear Editor,
discontinue therapy with sustained multi-year remission and an apparent cure of their AML.
Introduction Hypomethylating agents (HMAs), such as decitabine and azacitidine, have long been considered low-intensity, palliative treatments for patients with acute myeloid leukemia (AML) and are a standard approach for those patients not fit for intensive induction chemotherapy. Azacitidine has been shown to increase overall survival in elderly patients compared with conventional care and other less intensive regimens with a median duration of response of 10.4 months [1]. Different schedules of decitabine have also been examined, and a phase 2 study reported a better overall response rate of 64% with a 10-day schedule [2]. A more recent study reported on a higher rate of response among patients with TP53 mutations [3]. However, these responses were not considered durable with median duration of response of about 11 months. We herein report on 8 patients from three different academic centers with longer than expected response duration to decitabine or azacitidine, two of whom were able to Novelty This is the first report to describe prolonged and sustained remissions in patients with acute myeloid leukemia after limitedduration therapy with hypomethylating agents. We attempt to characterize patients who have achieved long-term remissions with hypomethylating agents in this report. * Joseph E. Maakaron [email protected] 1
Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, MMC 480, Minneapolis, MN 55455, USA
2
The Ohio State University, Columbus, OH, USA
3
Stanford School of Medicine, Stanford, CA, USA
4
University of North Carolina, Chapel Hill, NC, USA
Methods This is a retrospective case series looking at the clinical and pathological characteristics of patients who had exceptional responses to hypomethylating agents. We examined past clinical trial records and queried investigators for patients at our institutions who have been in complete remission (CR) for greater than 2 years with decitabine or azacitidine monotherapy. Clinical, pathological, and molecular data was recorded as available. Averages and standard errors were computed. This study was IRB approved at all the institutions involved.
Results Eight patients (5 female; 3 male) who experienced CR for over 2 years were identified. The average age at diagnosis was 66 years (range 50–76). Average presenting white blood cell (WBC) count was 38 × 103/mm3 (1.3–200). Five patients had de novo AML, two patients had secondary AML, and one patient had leukemia cutis, with average presenting bone marrow blast percentage o
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