Blood cells.

The FDA has approved omidubicel-onlv (Omisirge®, Gamida Cell Ltd.) for treatment of adult and pediatric patients 12 and older with hematologic malignancies, to minimize the time to neutrophil recovery and incidence of infection following myeloablative conditioning for umbilical cord transplantation.

Approved population: adults and pediatric patients ≥12 with hematologic malignancies

Why it matters: "Early-phase studies have demonstrated that ex vivo expansion of umbilical cord blood (UCB) stem cells before transplantation has the potential to address [delayed hematopoietic recovery]," wrote Mitchel E. Horwitz, Cellular Therapy Specialist and Stem Cell Transplant Specialist at Duke Health's Blood Cancer Center, and colleagues, in their publication of Study P0501 (NCT02730299), on which approval was based. "By expanding both hematopoietic stem and progenitor cells, the time to neutrophil recovery after myeloablative conditioning can be even more rapid than the time after a mobilized peripheral blood stem cell (PBSC) graft."

What they studied: Safety and efficacy were evaluated in the open-label, multicenter, phase 3 trial in which 125 patients were randomized 1:1 to receive either omidubicel-onlv transplantation or standard umbilical cord blood transplantation (UCBT), both following myeloablative chemotherapy consisting of total body irradiation–based or chemotherapy-based options. Treatment arms were well-balanced in demographics and baseline characteristics and were racially diverse. The primary end point measured was time to neutrophil recovery, with a secondary end point of incidence of grade 2/3 bacterial or grade 3 fungal infections within 100 days following transplantation.

What they found:

• The median time to neutrophil recovery was 12 days for those in the omidubicel-onlv arm, with 87% of patients achieving neutrophil recovery, compared with 22 days in the UCBT arm and 83% achieving neutrophil recovery
• The incidence of grade 2/3 bacterial or grade 3 fungal infections within 100 days following transplantation was 39% in the omidubicel-onlv arm compared with 60% in the UCBT arm

Adverse events: Adverse events experienced by those receiving omidubicel-onlv for any disease included acute and chronic graft-versus-host disease (GVHD) (58% and 35%, respectively), infusion reactions (47%), and graft failure (3%). Among the patients with hematologic malignancies enrolled in the study, the most common grade 3-5 adverse events were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%). Patients being treated should be monitored for signs and symptoms of infusion reactions, GVHD, engraftment syndrome, graft failure, and transmission of serious infections or rare genetic diseases from the donor cells, as well as for the rest of their life for potential secondary malignancies.

What's next: Future studies will address limitations and pressing questions such as the performance of omidubicel-onlv transplantation after reduced intensity conditioning and the comparative outcomes to other graft sources and specific disease types.

Conclusion: "Hematopoietic recovery after transplantation with omidubicel was faster, reduced early transplant-related complications, and reduced the number of days patients were hospitalized compared with standard UCBT," concluded Dr. Horwitz and colleagues. "The results of this trial demonstrate that omidubicel represents a major therapeutic advance and should be considered as a new standard of care for adult patients eligible for UCBT."

Instructions: The recommended dosage of omidubicel-onlv is two sequential infusions consisting of a cultured fraction and a non-cultured fraction:

1. Starting with the cultured fraction, which should be a minimum of 8.0 × 10⁸ total viable cells with a minimum of 8.7% CD34-positive cells and a minimum of 9.2 × 10⁷ total CD34-positive cells
2. Followed by a non-cultured fraction, which should be a minimum of 4.0 × 10⁸ total viable cells with a minimum of 2.4 × 10⁷ CD3-positive cells

For More Information

US Food and Drug Administration (2023). FDA approves omidubicel to reduce time to neutrophil recovery and infection in patients with hematologic malignancies. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-omidubicel-reduce-time-neutrophil-recovery-and-infection-patients-hematologic

Image credit: Bruce Wetzel & Harry Schaefer. Licensed under Public Domain.