Efficacy of Omidubicel vs Standard Umbilical Cord Blood Transplantation for Patients With GVHD

Mitchell E. Horwitz, MD, Professor of Medicine, Duke University Medical Center, Duke Cancer Institute, Durham, North Carolina, highlights a phase 3 trial on the efficacy of omidubicel compared with standard umbilical cord blood (UCB) transplantation for patients with graft-versus-host disease (GVHD).

Transcript:

Hello. My name is Dr. Mitchell Horwitz. I'm a professor of medicine and director of the Adult Blood and Marrow Transplant Program at Duke University Medical Center, in the Duke Cancer Institute.

Oncology Learning Network: What existing data led you and your co-investigators to conduct this research?

Dr Horwitz: This study was born out of a pilot study, done at both Duke University and Loyola Medical Center in Chicago that demonstrated that omidubicel, which is an ex vivo expanded UCB stem cell product, could provide long term robust hematopoietic engraftment following myeloablative bone marrow conditioning.

This early pilot study led to a multicenter phase 2 study of omidubicel. Transplanted as a single standalone stem cell graft, following myeloablative conditioning.

This is unprecedented because a manipulated stem cell graft had never been transplanted in patients.

This showed that omidubicel could be transplanted with efficacy and safety, and led to the phase 3 study that we're discussing today.

OLN: Please briefly describe your study and its findings.

Dr Horwitz: The phase 3 study of omidubicel versus standard UCB transplantation took place at multiple centers around the country. In fact, around the world.

The trial was designed to compare, as a primary endpoint, to neutrophil recovery, in patients receiving the standard cord blood transplant versus omidubicel.

Taking into account the fact that neutrophil recovery is particularly slow following standard cord blood transplantation, and results of the preliminary studies, we were gratified to see what we expected, which was that omidubicel reduced the time to neutrophil recovery from 22 days in standard cord blood transplantation down to 11 days in recipients of omidubicel.

As secondary endpoints, we looked at time to platelet recovery, which was also shorter in recipients of omidubicel.

The days spent outside the hospital was considerably longer for patients receiving omidubicel.

We looked at the incidence of severe bacterial and fungal infections. We found that the more rapid neutrophil recovery did lead to a reduction in severe bacterial and fungal infections. We were gratified to see that as well.

OLN: Were any of the outcomes particularly surprising?

Dr Horwitz: The preliminary studies did suggest that's what we were going to see. What was particularly surprising though, was that we found a reduction in the incidence of viral infections in recipients of omidubicel.

Protection from viral infections is felt to be a consequence of recovery of the lymphoid arm of the immune system. There was no reason to think that omidubicel would, in fact, do that, but we did see reductions in viral infections, considerable reduction, and we're looking into reasons to explain this.

We suspect that the large stem cell graft provided by omidubicel did in fact lead to early lymphoid recovery, in particular subsets of lymphocytes. We hope to have more data to explain that in the coming months.

OLN: What are the possible real-world applications of these findings in clinical practice?

Dr Horwitz: The study clearly shows superiority of omidubicel over standard cord blood transplantation.

We can make a case for the use of omidubicel should replace standard cord blood transplantation, given the rapid neutrophil recovery and the long term safety and robust hematopoiesis that we've seen in long term follow up studies of the graft.

This recovery of neutrophils in the as-treated population of the study, 10 days is really unprecedented in the whole field of hematopoietic stem cell transplantation.

This makes a case for possibly omidubicel being prioritized over other types of adult donor grafts, simply because of this favorable impact on not only post-transplant infections, but hospitalization and quality of life impacts on the rapid recovery.

OLN: Do you and your co-investigators intend to expand upon this research? If so, what are/will be your next steps?

Dr Horwitz: The sponsor of the study, Gamida Cell, who is the inventor of omidubicel, is now making plans for BLA submission, both in the United States and in Europe with the hopes of gaining approval for omidubicel and allowing us to not only use this in the standard of care clinical setting, but also to further study the graft and potentially compare it to other graft sources.

Current data suggests that with use of standard (graft-versus-host disease) GVHD prophylactic strategies, GVHD, which is one of the major complications of stem cell transplantation, is not impacted by the use of omidubicel. So we still see both acute and chronic GVHD.

Future studies I'd like to address using more contemporary GVHD prophylactic strategies, such as the use of posttransplant cyclophosphamide, which up till now has been rather risky in the setting of cord blood transplantation.

But with this large stem cell dose, I think it's feasible. That may address the problems of GVHD, which plague all types of stem cell transplant procedures.

OLN: Is there anything else pertaining to your research and findings that you would like to add?

Dr Horwitz: I would just like to add that for those in the field of stem cell transplantation, everyone is aware of the major increase in the use of half-matched or haploidentical stem cell transplants from related donors for patients who don't have a fully matched donor in either the family or in the national marrow donor program, Be The Match Registry.

I feel that the outcomes of this study justify the use and the further study of omidubicel and the setting of myeloablative transplantation needs to be compared to other graft sources, particularly the haploidentical graft source.

It's never been studied before, in this particular clinical scenario. Hopefully with approval of the graft and wider use and more experience in the transplant community, these studies could be done sometimes soon.