Single Center Experience with the Use of Hypomethylating Agents in Combination with Donor Lymphocyte Infusions As Initial Salvage Therapy Post Allogeneic Stem Cell Transplant in Relapsed AML/MDS/MPN

Abstract

Topic Significance & Study Purpose/Background/Rationale Relapsed acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) following an allogeneic stem cell transplant has a bleak prognosis with no standard for treatment identified. Current literature suggests combining hypomethylating agents (HMA) with a donor lymphocyte infusion (DLI) as salvage therapy to reduce disease burden and induce a graft versus leukemia (GVL) effect. At our institution, this salvage therapy option is being used for this population, peaking interest in our experience to date. Methods, Intervention, & Analysis We retrospectively analyzed this salvage regimen with a data cutoff of May 21, 2019. We looked at the patient's treated with HMA and DLI as first line for relapsed AML, MDS, or MPN following an allogeneic stem cell transplant. The planned treatment algorithm was 2 cycles of HMA followed by DLI and repeat for up to one year. This schedule varied depending on physician preference, availability of donor cells, and presence of GVHD (Graft versus host disease). Overall response rate and progression free survival (PFS) at two years were the primary objectives. Secondary objectives were the incidence and severity of GVHD and the toxicity profile of this treatment. Findings & Interpretation Our review identified eighteen evaluable patients with AML, MDS, and MPN with relapsed disease after an allogeneic transplant. Patients received a mean of seven cycles of HMA and an average of two DLIs. PFS at two years with this therapy was 28%. Of those who experienced GVHD, three were severe, four moderate, and five mild. Toxicities most commonly reported included fatigue, pancytopenia, and infection. Discussion & Implications The patients analyzed received HMA and DLI as their initial salvage therapy after failing allogenic transplant. Our analysis noted a Complete Response (CR) rate of 61% (several patients had additional therapies added to help them achieve a CR). Three patients relapsed prior to two years and three patients experienced non-relapse related mortality, leaving the PFS at 28%, suggesting the treatment induces remission, but the durability is in question. GVHD was mostly mild which supports the lower toxicity profile and provides an effective treatment option as initial salvage therapy, specifically for patients not considered medically fit to undergo intensive re-induction.