Posttransplant immunotherapy with a GM-CSF-based tumor vaccine following autologous stem cell transplant (ASCT) for acute myeloid leukemia (AML)

Abstract

6545 Background: Preclinical models have demonstrated the efficacy of GM-CSF secreting cancer vaccines accompanied by vaccine-primed lymphocyte infusion following ASCT. Methods: Patients ≤ 60 years old with de novo AML (excluding M3) were enrolled. Leukemia cells were harvested at diagnosis followed by induction and consolidation chemotherapy and ASCT. A pretransplant vaccine composed of irradiated autologous leukemia cells mixed with GM-CSF gene-modified K562 cells (K562/GM) was given followed by collection of vaccine-primed lymphocytes that were reinfused with the stem cell graft. Posttransplant vaccinations were initiated at week 6 (or upon platelet engraftment) and given every 3 weeks (10x107 tumor cells + 4x107 K562/GM cells) x 8 vaccinations. Results: Leukemia cell harvest was successful in 44/45 patients (blood draw 17, leukapheresis 24, bone marrow aspirate 4). To date, 34/41 patients (83%) have obtained a complete remission (CR) with induction chemotherapy, 17 have received the pretransplant vaccination, and 8 have initiated posttransplant vaccinations. Vaccines have been well tolerated with evidence of local injection site reactions in 16/17 patients. Delayed-type hypersensitivity (DTH) reactions to irradiated autologous tumor were negative pre-vaccination in 14/16 and converted to positive in 3/5 to date following 4 posttransplant vaccinations. Minimal residual disease (MRD) is being monitored by quantitative analysis of peripheral blood (PB) and bone marrow (BM) for WT1, a leukemia-associated gene, by RT-PCR. All patients had persistently detectable WT1 transcripts in PB and BM at enrollment. Most patients in CR analyzed to date had detectable WT1 transcripts in BM following induction (27/27), consolidation (14/15), and ASCT (4/6). A decrease in WT1 levels in BM was noted in 8/12 following the pretransplant vaccination. Conclusions: Collection of large quantities of autologous leukemia cells for vaccine production is feasible. Analysis of MRD by WT1 RT-PCR, in addition to immune response, may serve as a useful surrogate marker of efficacy in patients vaccinated in remission. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Gensys Cell Genesys Cell Genesys