Panobinostat and decitabine prior to donor lymphocyte infusion in allogeneic stem cell transplantation

Burak Kalin, Yvette van Norden, Michel van Gelder, Dimitri Breems, Johan Maertens, Mojca Jongen-Lavrencic, Annoek E. C. Broers, Eric Braakman, Tim Grob, Wendelien Zeijlemaker, Gert J. Ossenkoppele, Ellen Meijer, Jan J. Cornelissen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

Abstract

Outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is adversely affected by relapse to a considerable degree. To exploit the graft-versus-leukemia effect more effectively, we assessed the feasibility of early initiation of epigenetic therapy with panobinostat and decitabine after allo-HSCT and before donor lymphocyte infusion (DLI) in poor-risk patients with acute myeloid leukemia (AML) or refractory anemia with excess blasts with International Prognostic Scoring System score >= 1.5. A total of 140 poor-risk patients with AML aged 18 to 70 years were registered, and 110 proceeded to allo-HSCT. Three dose levels were evaluated for dose-limiting toxicities, including panobinostat monotherapy 20 mg at days 1, 4, 8, and 11 of a 4-week cycle (PNB mono group) and panobinostat combined with either decitabine 20 mg/m(2) (PNB/DAC20 group) or decitabine 10 mg/m(2) (PNB/DAC10 group) at days 1 to 3 of every 4-week cycle. After phase 1, the study continued as phase 2, focusing on completion of protocol treatment and treatment outcome. PNB mono and PNB/DAC10 were feasible, whereas PNB/DAC20 was not related to prolonged cytopenia. Sixty of 110 patients who underwent transplantation were eligible to receive their first DLI within 115 days after allo-HSCT. Grade 3 and 4 adverse events related to panobinostat and decitabine were observed in 23 (26%) of the 87 patients, and they received epigenetic therapy. Cumulative incidence of relapse was 35% (standard error [SE] 5), and overall survival and progression-free survival at 24 months were 50% (SE 5) and 49% (SE 5). Post-allo-HSCT epigenetic therapy with panobinostat alone or in combination with low-dose decitabine is feasible and is associated with a relatively low relapse rate. The trial was registered at the European Clinical Trial Registry, https://www. clinicaltrialsregister.eu, as ECT2012-003344-74.

Original languageEnglish
Pages (from-to)4430-4437
Number of pages8
JournalBlood advances
Volume4
Issue number18
DOIs
Publication statusPublished - 22 Sep 2020

Keywords

  • ACUTE MYELOID-LEUKEMIA
  • BONE-MARROW-TRANSPLANTATION
  • ACUTE MYELOGENOUS LEUKEMIA
  • RESIDUAL DISEASE DETECTION
  • POSTTRANSPLANTATION CYCLOPHOSPHAMIDE
  • SINGLE-AGENT
  • HEMATOLOGIC MALIGNANCIES
  • MAINTENANCE THERAPY
  • AML
  • PROPHYLAXIS

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