Azacitidine with or without Entinostat for the treatment of therapy-related myeloid neoplasm

Further results of the E1905 North American Leukemia Intergroup study

on behalf of the Eastern Cooperative Oncology Group and North American Leukemia intergroup

Research output: Contribution to journalArticle

30 Citations (Scopus)

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/m2/d) +/- the histone deacetylase inhibitor entinostat (4 mg/m2/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.

Original languageEnglish (US)
Pages (from-to)384-391
Number of pages8
JournalBritish Journal of Haematology
Volume172
Issue number3
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Azacitidine
Second Primary Neoplasms
Leukemia
Therapeutics
Histone Deacetylase Inhibitors
entinostat
Acute Myeloid Leukemia
Appointments and Schedules
Survival

Keywords

  • Acute myeloid leukaemia
  • Azacitidine
  • Histone deacetylase inhibitor
  • Myelodysplasia
  • Therapy related

ASJC Scopus subject areas

  • Hematology

Cite this

Azacitidine with or without Entinostat for the treatment of therapy-related myeloid neoplasm : Further results of the E1905 North American Leukemia Intergroup study. / on behalf of the Eastern Cooperative Oncology Group and North American Leukemia intergroup.

In: British Journal of Haematology, Vol. 172, No. 3, 01.01.2016, p. 384-391.

Research output: Contribution to journalArticle

on behalf of the Eastern Cooperative Oncology Group and North American Leukemia intergroup. / Azacitidine with or without Entinostat for the treatment of therapy-related myeloid neoplasm : Further results of the E1905 North American Leukemia Intergroup study. In: British Journal of Haematology. 2016 ; Vol. 172, No. 3. pp. 384-391.
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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/m2/d) +/- the histone deacetylase inhibitor entinostat (4 mg/m2/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.",
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