Autologous Tumor Combined with a GM-CSF-Secreting Cell Line Vaccine (GVAX®) Following Autologous Stem Cell Transplant (ASCT) in Multiple Myeloma.

Background: Preclinical models have demonstrated enhanced cancer vaccine efficacy when administered early following ASCT and accompanied by vaccine-primed lymphocyte infusion.

Methods: Patients with untreated myeloma were enrolled and underwent a bone marrow harvest to obtain tumor cells for vaccine processing. Patients eligible for ASCT following induction chemotherapy received a pre-transplant vaccination followed by leukapheresis to collect “primed” lymphocytes that were reinfused with the stem cell graft. Eight post-transplant vaccinations were administered at 3-week intervals starting 6 weeks posttransplant. The vaccine formulation consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting K562 cells (CG9962) at a ratio of 5:2, respectively. Three dose levels were assigned (1, 4, and 10 x10⁷ tumor cells/vaccination) based on tumor cell yield from the bone marrow harvest.

Results: 22 patients underwent tumor harvest, 18 completed induction chemotherapy, and 16 proceeded to vaccination (1 at 1 x 10⁷,4 at 4x10⁷, and 13 at 10x10⁷) and ASCT. At baseline, the median b2 microglobulin was 4 (2–14) and 35% had an IgA subtype. No grade 3/4 vaccine-related toxicities were observed. Median time to neutrophil engraftment (>500) and platelet engraftment (>50K) was 10 days. Local vaccine injection site reactions were observed in all patients. Delayed-type hypersensitivity (DTH) reactions to injections of irradiated autologous tumor cells were induced in only 1/15 patients after 4 post-transplant vaccines, but 4/10 were positive at one year post transplant. Induction of autologous tumor-reactive antibodies as well as antibodies reactive against CG9962 cells was observed. In vitro studies have demonstrated the induction and adoptive transfer of tumor-specific cellular immune responses that can be followed throughout the post-transplant period. Reproducible serum GM-CSF levels were achieved with repeated vaccinations suggesting no increased clearance of CG9962 cells due to induction of an allogeneic immune response. Of the 16 patients that have completed the ASCT, there were 6 complete and 5 partial remissions, for an overall response rate of 69%. Three patients with rising paraprotein levels early post-transplant have demonstrated paraprotein declines following initiation of post-transplant vaccines, suggesting a possible vaccine-mediated effect.

Conclusions: These data demonstrate the feasibility of this vaccine approach and show the therapeutic potential of K562 GVAX® vaccination in the ASCT setting in multiple myeloma.