Improved Clinical Outcomes with Omidubicel versus Standard Myeloablative Umbilical Cord Blood Transplantation: Results of a Phase III Randomized, Multicenter Study
Year of Publication
Horwitz, Mitchell E; tiff, Patrick; Rezvani, Andrew R; Hwang, William Ying Khee; Karras, Nicole; Valcarcel, David; Koh, Liang Piu; Khaled yasser; Keating, Amy K; Segalovich, Irit; Sanz, Guillermo; Cutler, Corey; Brunstein, Claudio G; Hanna, Rabi; McGuirk, Joseph P; Lindemans, Caroline A; Maziarz, Richard T; Schiller, Gary J; Hammerschlak, Nelson; Frankfurt, Olga; Blackwell, Beth; Galamidi, Einat
Myeloablative Umbilical Cord Blood (UCB); Omidubicel; Transplantation
BACKGROUND The primary limitation of umbilical cord blood (UCB) transplantation is delayed engraftment which is associated with an increased risk of morbidity and mortality. Omidubicel is a cryopreserved allogeneic stem cell-based product comprised of ex vivo expanded UCB-derived CD34+ progenitor cells and non-expanded myeloid and lymphoid cells. A phase I/II study demonstrated robust hematopoietic reconstitution with omidubicel. We now report results of a phase III trial to evaluate the efficacy of omidubicel compared to standard UCB in subjects with hematologic malignancies. METHODS Subjects were randomized to omidubicel or standard UCB, stratified by age, center, disease risk index (DRI), and intention to use 1 or 2-unit UCB as control. Myeloablative conditioning was limited to either a chemotherapy-only or two TBI-based regimens. The primary endpoint was time to neutrophil engraftment (ANC>500). Secondary endpoints were platelet engraftment (>20,000) at 42 days (d), grade 2-3 bacterial or invasive fungal infection at 100d, and days alive and out of hospital in the first 100d. Comparisons were performed with an intent-to-treat (ITT) analysis. RESULTS Between Jan 2017 and Dec 2019, 125 subjects were randomized at 33 sites in 7 countries to omidubicel (n=62) versus standard single (33%) or double (67%) UCB (n=63). Median age was 41 (range 13-65); 58% were male; most with AML (48%) or ALL (34%). DRI was moderate in 42% and high in 34%. The study population was diverse with 16% Black, 14% Asian, 3% multiracial and 13% Latino subjects. Demographics and baseline characteristics were well-balanced across the two arms. Median follow-up is 10 months. Median CD34+ cell dose for omidubicel recipients was 8 x 106/kg (124-fold expansion) and 0.3 x 106/kg for the controls. Median time to neutrophil engraftment was 12d (95% CI 10-15) in those randomized to omidubicel and 22d (95% CI 19-25) in controls (p<0.001). Cumulative incidence of engraftment is shown in the figure. Omidubicel recipients had a higher incidence of 42d platelet engraftment (55% vs. 35%, p=0.028), a lower incidence of infections (37% vs. 57%, p=0.027), and spent more time out of hospital (median 61 vs. 48d, p=0.005) than controls. Cumulative incidence of grade III/IV aGvHD was 14% vs. 21% (p=0.3), 1y-cGvHD was 35% vs. 29% (p=0.6) for omidubicel and control, respectively. Non-relapse mortality at 180d was 11% vs. 22% (p=0.1), 1y-relapse was 27% vs. 20% (p=0.4), and 1y-overall survival was 73% vs. 62% (p=0.16) for omidubicel and control, respectively. CONCLUSION Hematopoietic recovery following omidubicel transplantation was faster than standard UCB transplantation and was associated with clinical benefit. It was also faster than that expected after a mobilized peripheral blood stem cell transplantation. These data demonstrate that omidubicel is a highly effective graft source for patients in need of allogeneic transplantation.