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

Abstract

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, then every 2 weeks × 3. Tacrolimus taper began after vaccine completion. A total of 123 patients were enrolled, 92 proceeded to HSCT, and 57 (GVAX, n = 30; placebo, n = 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 = .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 = .79), 63% vs 59% (P = .86), and 30% vs 37% (P = .51) for GVAX and placebo, respectively. Nonrelapse mortality at 18 months was 17% vs 7.7% (P = .18), grade II to IV acute GVHD at 12 months was 34% vs 12% (P = .13), and chronic GVHD at 3 years was 49% vs 57% for GVAX and placebo (P = .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.

• Authors: Vincent T Ho, Haesook T Kim, Jennifer Brock, Ilene Galinsky, Heather Daley, Carol Reynolds, Augustine Weber, Olga Pozdnyakova, Mariano Severgnini, Sarah Nikiforow, Corey Cutler, John Koreth, Edwin P Alyea, Joseph H Antin, Mahasweta Gooptu, Rizwan Romee, Roman Shapiro, Yi-Bin Chen, Jacalyn Rosenblatt, David Avigan, F Stephen Hodi, Glenn Dranoff, Catherine J Wu, Jerome Ritz, Robert J Soiffer
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 7 Pg. 2183-2194 (04 12 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 34807983 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Graft vs Host Disease (etiology, prevention & control)
• Granulocyte-Macrophage Colony-Stimulating Factor (therapeutic use)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Leukemia, Myeloid, Acute (drug therapy)
• Vaccination