GM-CSF Secreting Leukemia Cell Vaccinations after Allogeneic Reduced-Intensity Peripheral Blood Stem Cell Transplantation (SCT) for Advanced Myelodysplastic Syndrome (MDS) or Refractory Acute Myeloid Leukemia (AML).
Authors: Ho Vincent , Dranoff Glenn , Kim Haesook , Pasek Mildred , Cutler Corey , Alyea Edwin , Koreth John , Antin Joseph H. , Soiffer Robert J. 
Published: October 2019

Disease relapse is a frequent cause of treatment failure in patients undergoing reduced intensity allogeneic stem cell transplantation for advanced MDS and AML. Prior studies with GVAX, a cancer vaccine composed of irradiated autologous myeloblasts modified to secrete GM-CSF, suggested anticancer activity in MDS and AML after autologous SCT or in primary therapy. We investigated the feasibility and safety of administering GVAX after allogeneic SCT. Patients with MDS-RAEB or AML with >5% marrow blasts and with a donor matched at HLA-A,B, DRB1 were eligible. Prior to transplant, autologous myeloblasts were collected from the marrow or blood and transfected with an adenovirus vector bearing the GM-CSF gene to generate the GVAX vaccine. Patients were conditioned with fludarabine 30mg/m2/d IV days -6 to -3, and busulfan 0.8mg/kg IV q12H days -6 to -3 prior to allogeneic PBSC infusion. GVHD prophylaxis included tacrolimus and mini-methotrexate. GM-CSF (Leukine) 250 mg/m2 SC QD was administered from day +1 until neutrophil engraftment. GVAX was administered SC/ID weekly for the first three doses, then q2 weeks for the last three doses starting between day +30 to +45 if there was neutrophil recovery and no grade II-IV acute GVHD. Taper of tacrolimus began after vaccine completion. Eighteen patients (10 URD, 8 MRD) have been transplanted to date: 12 AML, 4 MDS/RAEB, 2 CML myeloid blast crisis. Median age was 63 (range, 41–71 years). Median marrow blast content at transplant was 31% (range, 6–91%). GVAX was successfully generated for all 18 patients. Median vaccine cell dose was 1.0 × 107 cells (range, 0.1–1.0 ×107), and median 24-hour GM-CSF secretion by the vaccine was 8.2 ng/ml/106 cells (range 0.4 – 195). Seven patients did not initiate vaccination due to: inadequate neutrophil recovery/leukemia progression (4); acute GVHD (2); sepsis/death (1). Two patients were recently transplanted and have not reached day 30 to start vaccination. Among 9 patients who received GVAX, vaccination was well tolerated. Mild injection site reaction with induration, erythema, or pruritus was the only common side effect. After vaccination, 1 patient developed grade II skin acute GVHD and 3 had cGVHD that resolved with steroids. Donor chimerism was not adversely affected by vaccination. Six of 9 patients who started GVAX are alive at a median follow up of 7.5 months post transplant (range 1–16 mos). These include 4 patients in complete remission (3 AML, 1 MDS-RAEB) between 5 and 16 months after transplant, and 2 patients with minimal persistent AML early after SCT. Four of 5 patients who completed 6 vaccines remain progression free. Histologic examination of vaccination and leukemia cell DTH sites revealed significant infiltration with inflammatory cells and eosinophils. These preliminary results suggest GVAX vaccination is safe and may have anticancer activity in patients with MDS/AML after reduced intensity allogeneic SCT.