Ten-Year Omidubicel Data Improves Survival in Hematologic Malignancies With HSCT

Omidubicel demonstrated long-term graft durability, preserved trilineage hematopoiesis, and immune competence at up to 10 years of follow-up, ultimately improving survival in patients with hematological malignancies receiving allogeneic hematopoietic stem cell transplantation.¹

Treatment with omidubicel led to no late cases of secondary graft failure beyond the 5 patients reported in the primary analysis and just 1 case (1%) of donor-derived myelodysplastic syndrome (MDS). These data are consistent with previous reports of donor-derived myeloid neoplasms after cord blood transplants (0.6%–2%).

A case of donor-derived acute myeloid leukemia (AML) was also observed in the control arm of the phase 3 trial(NCT02730299).

Omidubicel is an ex vivo expanded stem cell graft derived of umbilical cord blood (UCB). Previously, UBC has demonstrated faster engraftment, fewer infections, and shorter durations of hospitalization in a recent multicenter phase 3 trial. Additionally, the agent has demonstrated early benefits for patients.

In a multi-institutional pooled analysis, the long-term outcomes of omidubicel transplantation from 5 prospective clinical trials were reported and compared. In these 5 trials, patients with hematologic malignancies or sickle cell hemoglobinopathy who underwent hematopoietic stem cell transplantation with omidubicel between 2010-2020 were enrolled. Patients were excluded if they had full engraftment with an unmanipulated UCB.

Across 26 academic transplant centers around the world, 116 patients were enrolled and underwent omidubicel transplantation. Ninety-two patients received omidubicel as a standalone therapy and 24 patients received it along with an unmanipulated UCB.

The median age of patients enrolled was 42 years (range, 2-62). A total of 52% if participants were male, 39% were non-white, and 30% had high or very-high disease risk indices. The most common diseases among patients included AML (41%), ALL (27%), MDS (12%), and sickle cell disease (8%).

Myeloblative conditioning regimens and standard graft vs host disease prophylaxis with a calcineurin inhibitor and mycophenolate mofetil was administered to all patients enrolled.

After engrafting fully with an unmanipulated UCB, 11 patients were excluded from the trial. Among the 105 patients left in the study, 97 (93%) had engrafted fully with omidubicel, 5 (5%) had primary graft failure, 2 (2%) had mixed chimerism between omidubicel and UCB, and 1 patient was deemed unevaluable for engraftment. The overall median follow-up was 22 months (range, 0.3-122.5) and 35.7 months among survivors (range 11.7, 122.5).

The 3-year overall survival was 62.5% (95% CI, 51.8-71.4) and the disease-free survival was 54.0% (95% CI, 43.0-63.7), respectively. Three-year cumulative incidences of chronic GVHD and disease relapse were 36.7% (95% CI, 27.0–46.5) and 24.0% (95% CI, 14.3–31.1), respectively. Most of the chronic GVHD cases were mild (54%). Moderate GVHD was seen in 33% of patients and 13% had severe disease. However, no deaths were attributed to GVHD.

Durable trilineage hematopoiesis was observed for up to 10 years and the median numbers of lymphoid subsets, including CD3+, CD4+, CD8+ T cells, CD19+ B cells, and CD16+/CD56+ NK cells were maintained within normal range for up to 8 years.

While secondary graft failure was noted in 5 patients, 3 of whom underwent a second allogeneic hematopoietic stem cell transplant, there were no late graft failures that occurred beyond what had been previously reported.

For secondary hematologic malignancies, investigators found donor-derived myeloid neoplasm in 1 patient with AML at 40 months post-transplant and post-transplant lymphoproliferative disorder (PTLD) in 2 patients at 17 and 20 months. One death was attributed to PTLD and there was 1 case of donor-derived myeloid neoplasm in the control UCB group of the phase 3 study.

_REFERENCE:

_{Lin C, Schwarzbach A, Montesinos P, et al. Multicenter long-term follow-up of allogeneic hematopoietic cell transplantation with omidubicel: a pooled analysis of five prospective trials. Presented at: 10th Annual Meeting of the Society of Hematologic Oncology (SOHO 2022); September 28-October 1, 2022; Houston TX.}