GM-CSF secreting leukemia cell vaccination for MDS/AML after allogeneic HSCT: a randomized, double-blinded, phase 2 trial

Vaccination using irradiated, adenovirus transduced autologous myeloblasts to secrete granulocyte-macrophage colony-stimulating factor (GVAX) early after allogeneic hematopoietic stem cell transplantation (HSCT) can induce potent immune responses. We conducted a randomized phase 2 trial of GVAX after HSCT for myelodysplastic syndrome with excess blasts or relapsed/refractory acute myeloid leukemia. Myeloblasts were harvested before HSCT to generate the vaccine. Randomization to GVAX vs placebo (1:1) was stratified according to disease, transplant center, and conditioning. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate. GVAX or placebo vaccination was started between day 30 and 45 if there was engraftment and no GVHD. Vaccines were administered subcutaneously/intradermally weekly 3 3, then every 2 weeks 3 3. Tacrolimus taper began after vaccine completion. A total of 123 patients were enrolled, 92 proceeded to HSCT, and 57 (GVAX, n 5 30; placebo, n 5 27) received at least 1 vaccination. No Common Toxicity Criteria grade 3 or worse vaccine-related adverse events were reported, but injection site reactions were more common after GVAX (10 vs 1; P 5.006). With a median follow-up of 39 months (range, 9-89 months), 18-month progression-free survival, overall survival, and relapse incidence were 53% vs 55% (P 5.79), 63% vs 59% (P 5.86), and 30% vs 37% (P 5.51) for GVAX and placebo, respectively. Nonrelapse mortality at 18 months was 17% vs 7.7% (P 5.18), grade II to IV acute GVHD at 12 months was 34% vs 12% (P 5.13), and chronic GVHD at 3 years was 49% vs 57% for GVAX and placebo (P 5.26). Reconstitution of T, B, and natural killer cells was not decreased or enhanced by GVAX. There were no differences in serum major histocompatibility chain-related protein A/B or other immune biomarkers between GVAX and placebo. GVAX does not improve survival after HSCT for myelodysplastic syndrome/acute myeloid leukemia. This trial was registered at www.clinicaltrials.gov as #NCT01773395.

Automated summary

This study examined the use of GVAX vaccine after allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome/acute myeloid leukemia. Results showed that GVAX did not improve survival rates. The vaccine did not affect the reconstitution of immune cells nor showed significant differences in immune biomarkers compared to placebo.