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GM-CSF secreting leukemia cell vaccination for MDS/AML after allogeneic HSCT: a randomized, double-blinded, phase 2 trial.
- Source :
-
Blood advances [Blood Adv] 2022 Apr 12; Vol. 6 (7), pp. 2183-2194. - Publication Year :
- 2022
-
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.<br /> (© 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.)
Details
- Language :
- English
- ISSN :
- 2473-9537
- Volume :
- 6
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Blood advances
- Publication Type :
- Academic Journal
- Accession number :
- 34807983
- Full Text :
- https://doi.org/10.1182/bloodadvances.2021006255