Omidubicel-Onlv for Allogeneic Transplantation (allo-HCT) in Patients with Hematologic Malignancies: Results of a Multicenter Open Label Expanded Access Program
Authors: Horwitz Mitchell , Tsai Stephanie B. , Rezvani Andrew R. , Maziarz Richard T , Goshen Uri , Levy Stuart , Schwarzbach Aurelie , Mazor Roei D. , Stiff Patrick J. , Schiller Gary J. 
Published: December 2023

Introduction
Omidubicel-onlv is a nicotinamide-modified allogeneic hematopoietic progenitor cell therapy donor source derived from umbilical cord blood (UCB). A phase 3 randomized study (NCT02730299) demonstrated improved hematopoietic recovery and decreased infections in patients transplanted with omidubicel compared to UCB. An expanded access program (EAP) was conducted to provide access to omidubicel in advance of commercial availability in the United States (US) in April 2023.
Objective
This was an open-label, single-arm EAP evaluating clinical outcomes in patients with hematologic malignancies following allo-HCT with omidubicel.
Methods
Eligible patients (≥12 years) with hematologic malignancies received myeloablative conditioning, prophylactic medications, and supportive care as per institutional guidelines. Patients were monitored for neutrophil and platelet engraftment, infections, graft versus host disease (GVHD), and additional clinical events for up to 2 years post-transplantation. Results were retrospectively compared with previously described outcomes in patients from the phase 3 study comparing transplant with omidubicel (P3-OMI, n=52) and unmanipulated UCB (P3-UCB, n=56).
Results
Between July 2020 and April 2023, 36 patients were enrolled and 29 (18 males, 11 females) were transplanted at 5 US sites. Median age was 39 years (range: 20-73); 55% were White, 21% Asian, 17% Black, and 7% other. Diagnoses were acute myelogenous leukemia (38%), acute lymphocytic leukemia (28%), myelodysplastic syndrome (21%), and other (14%). All patients received myeloablative conditioning (total body irradiation-based: 58.5%, chemotherapy alone: 34.5%). Median transplanted CD34+ cell dose was 5.6x10 6 cells/kg (range: 1.8-18.7x10 6 cells/kg) and HLA match was 4/6 in 52%, 5/6 in 45%, and 6/6 in 3%.
Median follow-up was 6.3 months (range: 0.3-27.7). No infusion reactions were reported. Median time to neutrophil (≥500/µl x3 days) and platelet (&gt;20,000/µl x3 days) engraftment were 13 and 34 days, respectively. Primary graft failure occurred in 2 (6.9%) patients, both alive &gt;100 days after second haploidentical transplant. The incidences of first grade 2-3 bacterial and invasive (grade 3) fungal infection through 100 days post-transplant were 16.9% and 0%, respectively. The incidence of grade 3 viral infections 1-year post-transplant was 13.4%. At 100 and 365 days post-transplant, disease-free survival (DFS) rates were 95.2% and 82.5%, and overall survival (OS) rates were 96.3% and 84.2%, respectively.
Acute GVHD was reported in 13 (44.8%) patients (grade 2: 34.5%, grade 3: 10.3%) and mild chronic GVHD in 1 (3.5%) patient. There were 4 deaths (13.8%): 2 due to relapse (Days 275 and 381), 1 due to infection (Day 135) and 1 due to respiratory failure (Day 10). Post-transplant lymphoproliferative disease was reported in 1 patient.
Demographic and disease characteristics were similar to those in the phase 3 omidubicel registration trial, including racial and ethnic diversity (&gt;39% minorities). Neutrophil engraftment time in EAP patients was similar to P3-OMI (10 days) and shorter than P3-UCB (20.5 days). Similarly, median platelet recovery was similar to P3-OMI (37 days) and shorter than P3-UCB (50 days). Infection, GVHD, DFS, and OS in EAP were also similar to those observed in P3-OMI (Table 1).
Conclusion
In a real-world EAP setting, the outcomes of allo-HCT with omidubicel in patients with hematologic malignancies were consistent with those from the phase 3 registration study. These data support the role of omidubicel as a donor source, particularly for patients from diverse racial backgrounds.