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

Author:

Ho Vincent T1,Kim Haesook T1,Brock Jennifer1,Galinsky Ilene2,Daley Heather1,Reynolds Carol G1,Weber Augustine1,Pozdnyakova Olga3ORCID,Severgnini Mariano1,Nikiforow Sarah1,Cutler Corey S4,Koreth John1,Alyea Edwin P5,Antin Joseph H1,Gooptu Mahasweta6,Romee Rizwan7,Shapiro Roman M1,Chen Yi-Bin8,Rosenblatt Jacalyn9,Avigan David10,Hodi F Stephen1,Dranoff Glenn11,Wu Catherine J.12ORCID,Ritz Jerome1,Soiffer Robert J1

Affiliation:

1. Dana-Farber Cancer Institute, Boston, Massachusetts, United States

2. Dana Farber Cancer Institute, Harvard, Boston, Massachusetts, United States

3. Brigham and Women's Hospital, Boston, Massachusetts, United States

4. Dana Farber Cancer Institute, Boston, Massachusetts, United States

5. Division of Cell Therapies, Durham, North Carolina, United States

6. Dana- Farber Cancer Institute, Boston, Massachusetts, United States

7. Dana Farber / Harvard Medical School, Boston, Massachusetts, United States

8. Massachusetts General Hospital

9. Beth Isreael Deaconess Medical Center, Boston, Massachusetts, United States

10. Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

11. Novartis, Cambridge, Massachusetts, United States

12. Dana-Farber Cancer Institute; Harvard Medical School, Boston, Massachusetts, United States

Abstract

Vaccination using irradiated, adenovirus transduced autologous myeloblasts to secrete GM-CSF (GVAX) early after allogeneic hematopoietic stem cell transplantation (HSCT) can induce potent immune responses. We conducted a randomized phase II trial of GVAX after HSCT for MDS-EB or relapsed/refractory AML. Myeloblasts were harvested before HSCT to generate the vaccine. Randomization to GVAX vs. placebo (1:1) was stratified by disease, transplant center, and conditioning. GVHD prophylaxis included tacrolimus and methotrexate. GVAX or placebo started between day +30-45 if there was engraftment and no GVHD. Vaccines were administered SC/ID weekly x 3, then q2 wks x 3. Tacrolimus taper began after vaccine completion. 123 patients enrolled, 92 proceeded to HSCT, and 57 (GVAX 30, Placebo 27) received at least 1 vaccination. No CTC grade ≥ 3 vaccine related adverse events were reported, but injection site reactions were more common after GVAX (10 vs. 1, p=0.006). With a median follow up of 39 months (range, 9-89), 18-month PFS, OS and relapse incidence were 53% vs 55% (p=0.79), 63% vs. 59% (p= 0.86), and 30% vs. 37% (p=0.51) for GVAX and placebo, respectively. NRM at 18 months was 17% vs. 7.7% (p=0.18), Grade II-IV aGVHD at 12 months 34% vs. 12% (p=0.13), and cGVHD at 3 years 49% vs. 57% for GVAX and placebo, respectively, p=0.26. Reconstitution of T, B, and NK cells were not decreased or enhanced by GVAX. There were no differences in serum MICA/B or other immune biomarkers between GVAX and placebo. GVAX does not improve survival after HSCT for MDS/AML. (Clinicaltrials.gov identifier: NCT01773395)

Publisher

American Society of Hematology

Subject

Hematology

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