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

https://doi.org/10.1016/j.bbmt.2018.06.016Get rights and content
Under a Creative Commons license
open access

Highlights

  • Azacitidine post-transplant maintenance may promote a graft-versus-leukemia effect and reduce GVHD.

  • Extended oral CC-486 dosing may prolong epigenetic regulation post-allograft.

  • CC-486 post-transplant maintenance was associated with low rates of relapse and GVHD.

  • One-year relapse- and progression-free survival rate was 72% with 14-day CC-486 dosing.

  • Recommended dose is 200 mg daily for 14 days per 28-day cycle.

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 84 days 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 per cycle (200 mg, n = 3; 300 mg, n = 4) and 23 for 14 days per 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 evaluable patients, 6 (21%) relapsed or had progressive disease: 3 of 7 patients (43%) who had received 7-day dosing and 3 of 23 (13%) who had 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 rates were 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.)

Key Words

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

Cited by (0)

Financial Disclosure: See Acknowledgments on page 2023.