Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II
Hematology Disease Topics & Pathways:
Leukemia, Diseases, Lymphoid Malignancies
In this work, we investigated NPM1 specific immune responses but also responses against other leukemia associated antigens (LAA) like PRAME (P300), Wilms’ Tumor 1 (WT1) and RHAMM (R3) in an extended cohort. We investigated these immune responses in LSC/LPC using colony-forming immunoassays (CFI) and ELISpots. We examine whether immuncheckpoint inhibition using the anti-programmed death 1 (anti-PD-1) antibody might increase immune responses against stem cell like cells, comparing NPM1-mutated (NPM1mut) to NPM1 wildtype (NPM1wt) patients.
In AML NPM1mut patients, specific immune responses of cytotoxic T cells against the epitope NPM1 showed a mean reduction of colonies in CFI of 27%, for P300 of 38%, for WT1 of 32% and for R3 of 42%. NPM1wt patients showed a mean reduction of colonies in CFI of for P300 of 28%, for WT1 of 28% and for R3 of 41%. Results are comparable, for NPM1mut and NPM1wt patients, there were immune responses seen in all epitopes.
When adding the anti-PD-1 antibody to CFI, in NPM1mut patients the mean additional inhibition using NPM1 as target was 47%, and for the other epitopes: P300 23%, WT1 27% and R3 26%. For NPM1WT patients, the additional inhibition with the addition of anti-PD-1 to CFI was for P300 25%, for WT1 34% and for R3 23%.
For the NPM1 epitope, 8 of 10 NPM1mut patients showed an immune response and 3/10 showed reduction in CFI of > 50%. The NPM1 epitope displayed an additional reduction with anit-PD-1 in all 10 NPM1mut Patients and in 6 of 10 a reduction of > 50%. Thus, especially the NPM1 specific immune responses are strong in NPM1mut patients by adding anti-PD-1.
Taken together, the anti-PD-1 antibody increases specific T cell responses of LAA-stimulated CTL and the cytotoxic effect of T cells against LPC/LSC. The effect was strongest in NPM1mut patients against the immunogenic epitope derived from the mutational region of NPM1 and even stronger when adding anti-PD-1. These data suggest there could be a NPM1 mutation directed immunotherapeutic approach using LAA-directed vaccination strategies in NPM1-mutated AML and combination with anti-PD-1 antibodies might open new application possibilities.
Disclosures: Greiner: BMS: Research Funding. Schrezenmeier: Alexion Pharmaceuticals Inc.: Honoraria, Research Funding.
See more of: Oral and Poster Abstracts