Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study

Abstract

Omidubicel is an ex vivo expanded hematopoietic progenitor cell and nonexpanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We report results of a phase 3 trial to evaluate the efficacy of omidubicel compared with standard umbilical cord blood transplantation (UCBT). Between January 2017 and January 2020, 125 patients age 13 to 65 years with hematologic malignancies were randomly assigned to omidubicel vs standard UCBT. Patients received myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil for graft-versus-host disease (GVHD). The primary end point was time to neutrophil engraftment. The treatment arms were well balanced and racially diverse. Median time to neutrophil engraftment was 12 days (95% confidence interval [CI], 10-14 days) for the omidubicel arm and 22 days (95% CI, 19-25 days) for the control arm (P < .001). The cumulative incidence of neutrophil engraftment was 96% for patients receiving omidubicel and 89% for patients receiving control transplants. The omidubicel arm had faster platelet recovery (55% vs 35% recovery by 42 days; P = .028), had a lower incidence of first grade 2 to 3 bacterial or invasive fungal infection (37% vs 57%; P = .027), and spent more time out of hospital during the first 100 days after transplant (median, 61 vs 48 days; P = .005) than controls. Differences in GVHD and survival between the 2 arms were not statistically significant. Transplantation with omidubicel results in faster hematopoietic recovery and reduces early transplant-related complications compared with standard UCBT. The results suggest that omidubicel may be considered as a new standard of care for adult patients eligible for UCBT. The trial was registered at www.clinicaltrials.gov as #NCT02730299.

© 2021 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1

CONSORT diagram. Randomization and treatment of patients. CBU, cord blood unit.

Figure 2

Omidubicel and control cord blood graft characteristics. Median (range) for TNC content, CD34+ cell content, and CD34+ cell doses before and after ex vivo expansion of the UCB unit. Pre-expansion values represent cell content as reported by the cord blood bank before cryopreservation of the UCB unit. AT, as treated population.

Figure 3

Hematopoietic recovery. Analysis was performed in the as-treated population (n = 108). Cumulative incidence of neutrophil engraftment by day 42 (A) and platelet recovery by day 100 (B) among recipients of omidubicel or unmanipulated UCB.

Figure 4

Correlation of CD34+ cell content with neutrophil engraftment. Correlation of CD34+ total cell count and cell dose with time to neutrophil engraftment. (A) Regression of the time to engraftment on the total number of CD34+ cells (both on the natural logarithmic scale). The shaded interval is the pointwise 95% CI around the predicted log time. The regression line is log days to engraftment (5.70-0.50 log [106 total cells]). (B) Regression of the time to engraftment on the number of CD34+ cells per patient actual body weight (both on the natural logarithmic scale). The shaded interval is the pointwise 95% CI around the predicted log time. The regression line is log days to engraftment (4.30-0.42 log [105 cells per kg]).

Figure 5

GVHD. Cumulative incidence of grade 2 to 4 aGVHD (A), grade 3 to 4 aGVHD (B), and cGVHD (C). Analysis was performed in the transplanted population by randomly assigned treatment.

Figure 6

Outcomes of omidubicel and standard UCBT, ITT analysis. (A-B) Cumulative incidence of NRM (A) and relapse (B). (C-D) Probability of DFS (C) and OS (D). HR, hazard ratio.

Figure 7

Infections after transplantation. (A) Cumulative incidence of first grade 2 to 3 bacterial infection or invasive fungal infections during the first 100 days after transplantation for the ITT population. (B) Cumulative incidence of first grade 3 viral infection during the first year for the ITT population. All infection events that occurred after random assignment are accounted for in the analysis. (C) Relative risk (95% CI) for bacterial, viral, and all infections at 1 year after transplantation in the omidubicel and the standard UCB groups for the as-treated population. (D) Grade 1 to 3 viral infections at 1 year after transplantation by species for the as-treated population. CL, confidence level.