Epigenetic therapy may improve graft-versus-leukemia effect
Allogeneic hematopoietic stem cell transplantation (alloHSCT) can confer a graft-versus-leukemia (GVL) effect in patients with AML. Still, the relapse rate remains high, especially in poor-risk AML. The HOVON 116 study evaluated whether epigenetic therapy and donor lymphocyte infusion post alloHSCT could enhance the GVL-effect, as was presented by Dr Jan Cornelissen (Erasmus MC, Rotterdam, The Netherlands).
In this study 110 newly diagnosed patients with poor-risk AML underwent alloHSCT, and 87 of these patients subsequently received the histone deacetylase inhibitor panobinostat (PNB, 20 mg), either alone or combined with the demethylating agent decitabine (DCB, 10 or 20 mg/m2). Epigenetic therapy was interspersed with low dosage donor lymphocyte infusion.
In phase 1 of the study the combination of PNB with 20 mg/m2 DCB (n=13) resulted in prolonged cytopenia, which was a dose limiting toxicity, and was therefore considered as not feasible. Phase 2 continued with PNB alone (n=39) and PNB plus 10 mg/m2 DCB (n=35).
First, second and third DLI were achieved in 57%, 36% and 21% of patients, respectively. The primary endpoint, completion of treatment, was achieved in 55% of patients and was considered successful. Toxicities were limited, as was the incidence of GVDH. The PFS and RFS of the Hovon-116 cohort compared favorably to a historical cohort. Cornelissen: “These preliminary findings might suggest a reduction of relapse and, therefore, will be followed by an international prospective randomized study in (very) poor-risk AML patients.”