stem cell graft
Peripheral blood
LISBON—Phase 1 results suggest a programmed cellular therapy is safe for use in patients with hematologic malignancies.
The therapy, ProTmune, is being developed as a next-generation allogeneic graft intended to reduce the incidence and severity of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplant (HSCT).
Three of 7 patients who received ProTmune in this trial did develop acute GVHD, and 2 patients died.
However, the remaining 5 patients were still alive and disease-free at last follow-up.
There were no serious adverse events (AEs) attributed to ProTmune. The most common AEs were nausea, vomiting, and chest pain.
These results were presented at the 44th Annual Meeting of the EBMT (abstract A401*).
The trial, known as PROTECT, is sponsored by Fate Therapeutics, the company developing ProTmune.
The phase 1 portion of PROTECT enrolled 7 adults with hematologic malignancies—1 with myelodysplastic syndrome, 3 with acute lymphoblastic leukemia, and 3 with acute myeloid leukemia.
Patients were set to undergo matched, unrelated donor HSCT and received ProTmune as the graft. ProTmune is manufactured by modulating a mobilized peripheral blood graft with 2 small molecules, FT1050 and FT4145.
The patients ranged in age from 34 to 69, and most (n=5) were female. For conditioning, patients received fludarabine/busulfan (n=1), busulfan/cyclophosphamide (n=1), fludarabine/melphalan (n=3), or cyclophosphamide/total body irradiation (n=2).
Results
The data cut-off was February 26, 2018. The median time on study was 228 days (range, 151 to 353).
None of the patients had graft failure. The median time to neutrophil engraftment was 18 days (range, 14 to 22).
Three patients had acute GVHD at day 100 after HSCT. Two patients had grade 2 skin GVHD, and 1 had grade 3 GVHD in the skin and gut.
All 3 patients responded to steroid treatment. GVHD resolved in 5 days for the patient with grade 3 GVHD. For the grade 2 patients, GVHD resolved in 7 days and 8 days, respectively.
None of the patients relapsed, but 2 died—1 of pulmonary edema and 1 of atrial fibrillation.
AEs related to ProTmune included grade 1 vomiting (n=2), grade 2 nausea (n=2), and grade 2 chest pain (n=1).
Phase 2
The phase 2 portion of PROTECT is ongoing. This is a randomized, controlled, double-blinded trial designed to assess the safety and efficacy of ProTmune in up to 60 adults with hematologic malignancies undergoing matched, unrelated donor HSCT following myeloablative conditioning.
Patients are being randomized, in a 1:1 ratio, to receive either ProTmune or a conventional, mobilized peripheral blood cell graft from a matched, unrelated donor.
The primary efficacy endpoint is the cumulative incidence of grade 2-4 acute GVHD by day 100 post-HSCT. Rates of chronic GVHD, cancer relapse, disease-free survival, and overall survival are also being assessed.
*Some data in the abstract differ from the presentation.