Posttransplant Immunotherapy with a GM-CSF-Based Tumor Vaccine (GVAX®) Following Autologous Stem Cell Transplant (ASCT) for Acute Myeloid Leukemia (AML).

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 (CG9962) 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 CG9962 cells) x 8 vaccinations.

Results: Leukemia cell harvest was successful in 51/54 patients (blood draw − 22, leukapheresis − 28, bone marrow aspirate − 4). To date, 44/54 patients (81%) have achieved a complete remission (CR) following induction chemotherapy, 27 have received the pretransplant vaccination, and 15 have initiated posttransplant vaccinations. Local vaccine injection site reactions developed in all patients. Delayed-type hypersensitivity (DTH) reactions to irradiated, autologous tumor were induced post vaccination in 4/11. Antibodies reactive against autologous tumor were induced in 5/11 and against CG9962 cells in 10/10. 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 detectable WT1 transcripts in PB and BM at diagnosis. Most patients in CR had persistently detectable WT1 transcripts in BM following induction (92%), consolidation (91%), and ASCT (63%), whereas, clearance of WT-1 in PB was more frequent (49% detectable post induction, 50% post consolidation, and 31% post ASCT). A decrease in WT1 was noted in 67% (12/18 in the BM and 10/15 in PB) following the pretransplant vaccination.

Conclusions: Collection of large quantities of autologous leukemia cells for vaccine production is feasible. Reduction in WT-1 transcript levels following the pre-transplant vaccine suggests anti-leukemic activity of this GVAX® vaccine platform.