Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial

Research output: Contribution to journalArticle

Authors

  • Nadira Jilani
  • Shamyla Siddique
  • Sandeep Nagra
  • Janice Ward
  • Peter Hazlewood
  • Richard Buka
  • Paresh Vyas
  • Eleni Tholouli
  • Charles Crawley
  • Nigel Russell
  • Jenny Byrne
  • Ram Malladi
  • John Snowden
  • Mike Dennis

Abstract

Disease relapse is the major causes of treatment failure after allogeneic stem cell transplantation (SCT) in patients with acute myeloid leukemia (AML). As well as demonstrating significant clinical activity in AML, azacitidine (AZA) upregulates putative tumor antigens, inducing a CD8(+) T cell response with the potential to augment a graft-versus-leukemia effect. We, therefore, studied the feasibility and clinical sequelae of the administration of AZA during the first year after transplantation in 51 patients with AML undergoing allogeneic SCT. Fourteen patients did not commence AZA either because of transplantation complications or withdrawal of consent. Thirty-seven patients commenced AZA at a median of 54 days (range, 40 to 194 days) after transplantation, which was well tolerated in the majority of patients. Thirty-one patients completed 3 or more cycles of AZA. Sixteen patients relapsed at a median time of 8 months after transplantation. No patient developed extensive chronic graft-versus-host disease. The induction of a post-transplantation CD8(+) T cell response to 1 or more tumor-specific peptides was studied in 28 patients. Induction of a CD8(+) T cell response was associated with a reduced risk of disease relapse (hazard ratio [HR], .30; 95% confidence interval [CI], .10 to .85; P = .02) and improved relapse-free survival (HR, .29; 95% CI, .10 to .83; P = .02) taking into account death as a competing risk. In conclusion, AZA is well tolerated after transplantation and appears to have the capacity to reduce the relapse risk in patients who demonstrate a CD8(+) T cell response to tumor antigens. These observations require confirmation in a prospective clinical trial.

Details

Original languageEnglish
Pages (from-to)385–390
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number2
Early online date9 Sep 2015
Publication statusPublished - 1 Feb 2016

Keywords

  • Acute myeloid leukemia, Relapse, Azacitidine, Tumor antigens