Omidubicel Improves Outcomes, Reduces Hospital Stay for Patients with Hematologic Malignancies

Patients with hematologic malignancies who received umbilical cord blood transplantation with omidubicel engrafted faster, had fewer infections, and spent less time in the hospital, compared with patients who received a standard single or double umbilical cord blood graft, according to a recent study published in Blood.

“The findings provide a strong argument in favor of omidubicel as the new standard of care for patients who are candidates for umbilical cord blood transplantation,” said senior study author Mitchell Horwitz, MD, of Duke University Medical Center in Durham, North Carolina.

While omidubicel, which has yet to be approved for use, is not commercially available, “it will soon be considered for approval by the regulatory agencies in both the U.S. and the European Union,” noted Dr. Horwitz. “Once approved, it is my belief that all patients who are candidates for a mismatched, myeloablative allogeneic stem cell transplantation should be considered for an omidubicel graft.”

Dr. Horwitz and colleagues randomly assigned patients with hematologic malignancies to either omidubicel (n=62) or standard umbilical cord blood transplant using standard single or double grafts (n=63) to compare the efficacy of the approaches.

Additionally, participants received myeloablative conditioning and graft-versus-host disease (GVHD) prophylaxis with mycophenolate mofetil 15 mg/kg three times per day and a calcineurin inhibitor (tacrolimus at target trough levels 5-15 ng/ml or cyclosporine at target trough levels 200-400 ng/ml).

The median age of patients in the study was 41 years (range = 13-65) and the majority had either acute myeloid leukemia (48%) or acute lymphocytic leukemia (33%). Other malignancies included myelodysplastic syndromes, chronic myeloid leukemia, and lymphoma.

Patients in the omidubicel arm underwent transplant at a median of 41 days after randomization. In contrast, those in the standard cord transplant group underwent transplantation after a median of 26 days.

Median time to neutrophil engraftment – the primary endpoint of the study – was significantly shorter in the omidubicel group (12 vs. 22 days; p<0.001). By day 42 after transplant, the cumulative incidence of neutrophil engraftment was 96% at 10 days for omidubicel versus 89% at 20 days for the standard transplant (p<0.001).

Individuals assigned to omidubicel also had significantly faster platelet recovery (55% vs. 35% recovered by 42 days; p=0.028), lower incidence of first grade 2/3 bacterial or invasive fungal infections (37% vs 57%; p=0.027), and spent a greater median number of days out of the hospital during the first 100 days after transplant (61 vs. 48 days; p=0.005).

To date, omidubicel has not yet been transplanted after reduced intensity or non-myeloablative bone marrow conditioning. “Until such studies have been done,” said Dr. Horwitz, “[omidubicel] is recommended for patients receiving myeloablative conditioning.”

While these results show a benefit with omidubicel compared with a standard umbilical cord blood graft, Dr. Horwitz said it is still unclear how outcomes will compare to recipients of other graft sources, such as a haploidentical or matched unrelated donor stem cells.

The authors report no relevant conflicts of interest.

Reference

Horwitz ME, Stiff PJ, Cutler CS, et al. Omidubicel versus standard myeloablative umbilical cord blood transplantation: Results of a phase III randomized study [published online ahead of print, 2021 Jun 22.] Blood. doi: 10.1182/blood.2021011719.

These findings represent an important advance in improving the use of umbilical cord blood as a donor source, with key implications for making umbilical cord blood transplantation safer and more accessible, particularly in minority populations that may lack human leukocyte antigen (HLA)-matched donors.

While the increasing reliance on post-transplant cyclophosphamide has made haploidentical and mismatched unrelated donor transplants an increasingly effective and favored approach to transplant, there are currently several questions related to this patient population, including those concerning the optimal donor source.

Additional questions include those related to impacts on resource utilization, further understanding and optimization of immune reconstitution after omidubicel, and the role of minimal residual disease and risk of relapse.

Although the study did not demonstrate any statistically significant differences in GVHD or survival between omidubicel and standard umbilical cord blood transplant, it should be noted that the study was not powered to detect survival differences.

Betty Ky Hamilton, MD
Cleveland Clinic