Improved Clinical Outcomes with Omidubicel versus Standard Myeloablative Umbilical Cord Blood Transplantation: Results of a Phase III Randomized, Multicenter Study

Presentation

Authors:

URL:
https://tct.confex.com/tct/2021/meetingapp.cgi/Paper/17215

Keywords:
Myeloablative Umbilical Cord Blood (UCB); Omidubicel; Transplantation

Abstract:
<p>BACKGROUND<br /> 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.<br /> METHODS<br /> 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&gt;500). Secondary endpoints were platelet engraftment (&gt;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.<br /> RESULTS<br /> 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&lt;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.<br /> CONCLUSION<br /> 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.</p>