CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes

Research output: Contribution to journalArticle

Authors

  • Marcos De Lima
  • Betul Oran
  • Richard E. Champlin
  • Esperanza B. Papadopoulos
  • Sergio A. Giralt
  • Bart L. Scott
  • Basem M. William
  • Joel Hetzer
  • Eric Laille
  • Becky Hubbell
  • Barry S. Skikne

Colleges, School and Institutes

Abstract

Relapse is the main cause of treatment failure after allogeneic stem cell transplant (alloSCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Injectable azacitidine can improve post-transplant outcomes but presents challenges with exposure and compliance. Oral CC-486 allows extended dosing to prolong azacitidine activity. We investigated use of CC-486 maintenance therapy after alloSCT.

Adults with MDS or AML in morphologic complete remission at CC-486 initiation (42 to 84days after alloSCT) were included. Patients received 1 of 4 CC-486 dosing schedules per 28-day cycle for up to 12 cycles. Endpoints included safety, pharmacokinetics, graft-versus-host disease (GVHD) incidence, relapse/progression rate, and survival. Of 30 patients, 7 received CC-486 once daily for 7 days a cycle (200 mg, n = 3; 300 mg, n = 4) and 23 for 14 days a cycle (150 mg, n = 4; 200 mg, n = 19 [expansion cohort]). Grades 3 to 4 adverse events were infrequent and occurred with similar frequency across regimens. Standard concomitant medications did not alter CC-486 pharmacokinetic parameters. Three patients (10%) experienced grade III acute GVHD and 9 experienced chronic GVHD. Of 28 assessable patients, 6 (21%) relapsed or had progressive disease: 3 of 7 patients (43%) received 7-day dosing and 3 of 23 (13%) received 14-day dosing. Transplant-related mortality was 3%. At 19 months of follow-up, median overall survival was not reached. Estimated 1-year survival was 86% and 81% in the 7-day and 14-day dosing cohorts, respectively.

CC-486 maintenance was generally well tolerated, with low rates of relapse, disease progression, and GVHD. CC-486 maintenance may permit epigenetic manipulation of the alloreactive response postallograft. Findings require confirmation in randomized trials. (ClinicalTrials.gov NCT01835587.)

Details

Original languageEnglish
JournalBiology of Blood and Marrow Transplantation
Early online date20 Jun 2018
Publication statusE-pub ahead of print - 20 Jun 2018

Keywords

  • Maintenance therapy, Allogeneic stem cell transplantation, Myelodysplastic syndromes, Acute myeloid leukemia, CC-486