Panobinostat and decitabine prior to donor lymphocyte infusion in allogeneic stem cell transplantation.
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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/m2 (PNB/DAC20 group) or decitabine 10 mg/m2 (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.
SUBMITTER: Kalin B
PROVIDER: S-EPMC7509859 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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