INTRO: Omidubicel (Omi) is an ex vivo expanded hematopoietic progenitor cell product derived from a single umbilical cord blood (UCB) unit that was FDA approved in April 2023. In the Phase III trial (P3) comparing Omi transplant (HCT) to standard UCB transplant, overall aGVHD and cGVHD rates were similar between arms, though a subgroup analysis revealed a higher incidence of grade II-IV aGVHD among those receiving total body irradiation (TBI) compared to those receiving chemotherapy only based conditioning in the Omi group (Data Gamida-Cell). Here, we present our experience with Omi HCT to better characterize rates of GVHD in patients who received chemotherapy-only myeloablative conditioning (MAC) at Loyola University Medical Center (LUMC).

METHODS: We identified all patients who received Omi HCT at LUMC through participation in the P3 (PMID:34157093), the Expanded Access Protocol (EAP) (PMID:40204073) or as commercially available therapy following FDA approval between 12/2/17 and 7/1/24. All patients received conditioning with thiotepa, busulfan, and fludarabine. No patients received TBI or anti-thymocyte globulin. All received GVHD prophylaxis with mycophenolate mofetil and tacrolimus. Data was collected retrospectively from medical records. Descriptive statistics were computed and summarized around variables of interest.

RESULTS: Eighteen patients underwent Omi HCT at LUMC. Median age at transplant was 50 (42 – 64), 28% were female, and diseases were: AML (61%), ALL (11%), T cell leukemia/lymphoma (11%), MDS (11%), and CML (6%). Median time to neutrophil engraftment was 11.5 days (9.8-15.3) and median time to platelet engraftment was 34.5 days (28-49.3). Two patients failed to engraft but were successfully salvaged by haploidentical HCT. Median time to last follow up after transplant was 35 months (27.5-70.0). Fourteen (77.8%) were alive 1 year after transplant, and 11 (58.7%) were alive 2 years after. Disease relapse occurred in 7 patients (39%) – all with multiply relapsed or primary refractory disease. These were comparable to P3 and EAP outcomes.

Six patients (33%) developed aGVHD within 100 days of transplant, including 4 (22%) with grade 3-4 aGVHD. In the P3, Day 100 aGVHD was 56% with 14% Grade 3-4; in the EAP, reported rates were 63% and 19%. The mean age at time of transplant was 59 (+/- 12.7) in those with aGVHD and 49 (+/- 11.3) in those without. There did not appear to be a difference comparing aGVHD+ vs aGVHD- with respect to: mean age of donor cord blood (DCB) unit (7.33 (+/- 5.13) vs 6.58 (+/-4.08)), mean DCB CD34+ cell dose (12.02 +/-3.62 x 106 vs 12.06 +/-2.67 x 106), mean total nucleated cell (TNC) dose (2.48 +/-0.57 x 109 vs 2.43 +/-0.55 x 109), degree of HLA matching (5.17 +/-1.17 vs 5.25 +/-1.29), and donor and recipient CMV status mismatch (50% of each group).

Five patients (28%) developed cGVHD, 4 of these within 1 year of transplant. Three (17%) had mild, 1 had moderate (6%), and 1 (6%) had severe cGVHD. By comparison, the Phase 3 study reported a 1-year cGVHD rate of 35% with 27% mod-severe. The EAP reported 9% cGVHD; all mild. Mean age was 49 (+/- 12.13) in those with cGVHD and 54 (+/- 12.83) in those without. Notably, mean age of DCB unit was younger for those with cGVHD: 4.20 years (+/-2.77) in cGVHD+ vs 7.85 (+/- 4.45) in cGVHD-. There did not appear to be a difference comparing cGVHD+ vs cGVHD- with respect to: mean DCB CD34+ cell dose (13.50 +/-1.84 x 106 vs 11.49 +/- 3.10 x 109), mean TNC dose (2.54 +/- 0.40 x 109 vs 2.41 +/- 0.60 x 109), and degree of HLA match (4.80 +/- 1.48 vs 5.38 +/- 1.12). Donor-recipient CMV status was mismatched in 4/5 (80%) patients with cGVHD versus in 5/13 (38%) without.

One-year GVHD-free relapse-free survival (GRFS) was 33% and cGVHD-free relapse-free survival (cGRFS) was 50%, rates affected by relapse in high risk disease. The P3 reported a GRFS of 36% and the EAP a cGRFS of 66%.

CONCLUSION: Our practice with Omi HCT using exclusively chemo-only conditioning showed comparable outcomes with the pivotal P3 and with the EAP. However, rates of aGVHD appeared lower, and cGVHD was comparable to the lower rates in the EAP compared to the P3, in which 31/62 (50%) of patients in the Omni group received TBI. We did find increased cGVHD with CMV mismatch and younger DCB units, but not with other factors previously reported to affect GVHD rates in HCT. Our findings support use of a chemotherapy-only MAC prior to transplant with omidubicel.

This content is only available as a PDF.
2025
Sign in via your Institution