Azacitidine with or without Entinostat for the treatment of therapy‐related myeloid neoplasm: further results of the E1905 North American Leukemia Intergroup study
Year: 2015
Type: article
Abstract: Therapy-related myeloid neoplasms (tMN) are serious late effects of the treatment of cancer with poor response to conventional treatment. Azacitidine (AZA) has been used to treat patients with tMN but current data are retrospective. We present here 47 tMN patients prospectively enrolled as a specific cohort in the E1905 study. TheE1905 study was a randomized phase 2 study (NCT00313586) testing 10 d of AZA (50 mg/m(2) /d) +/- the histone deacetylase inhibitor entinostat (4 mg/m(2) /d PO day-3 and day-10). A total of 47 patients [29 therapy-related myelosyspastic syndrome (t-MDS) and 18 therapy-related acute myeloid leukaemia (t-AML)] were recruited to the study. 24 patients were treated with AZA monotherapy and 23 with AZA+entinostat. The median number of administered cycles was 4, significantly higher in patients treated with AZA (6 cycles vs. 3 cycles, P = 0·008). Haematological normalization rates were 46% in monotherapy and 17% in the combination arm. Median overall survivals were 13 and 6 months, respectively. The novel 50 * 10 schedule of azacitidine appears effective, with response rates, when given as single agent, comparable to those for patients with de novo MDS/AML treated on the same protocol. However, the combination of AZA and entinostat was associated with increased toxicity and could not be recommended for treatment of tMN.
Source: British Journal of Haematology
DOI: 10.1111/bjh.13832
Authors: Thomas Prebet, Zhuoxin Sun, Rhett P. Ketterling, Amer Zeidan, Peter Greenberg, James Herman, Mark Juckett, Mitchell R. Smith, Lisa Malick, Elisabeth Paietta, Magdalena Czader, Maria Figueroa, Janice Gabrilove, Harry P. Erba, Martin S. Tallman, Mark Litzow, Steven D. Gore, the Eastern Cooperative Oncology Group and North American Leukemia intergroup
Institutions: Yale Cancer Center, Yale University, Dana-Farber Cancer Institute, Mayo Clinic, Stanford Medicine, Stanford University, Johns Hopkins University, University of Wisconsin–Madison, Cleveland Clinic, Montefiore Medical Center, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, University of Michigan, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, U-M Rogel Cancer Center, Memorial Sloan Kettering Cancer Center, Mayo Clinic Comprehensive Cancer Center (Minnesota)
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1347238333, G1545560008, G1591967931, ECOG-ACRIN Network Group Operations Center, G1938688226, Network Lead Academic Participating Site: Memorial Sloan-Kettering Cancer Center, G2043432835, G2368829511, G2496008249, G2679961467, G2845356120, Targeting Epigenomics in Myeloid Neoplasms, G3475623468, G36541222, SWOG Network Group Operations Center of the NCTN, G5417201949, G5566132837, ECOG-ACRIN Network Group Statistics and Data Management Center, G7484487955, Eastern Cooperative Oncology Group Operations Office, G8463080816, National Clinical Trials Network Research at the University of Wisconsin
OpenAlex ID: W2178087063