Novel Therapy Boosts Survival After Stem Cell Transplants

Multipotent stem cells in the bone marrow: © Juan Gärtner - stock.adobe.com

In the field of hematopoietic cell transplantation (HCT), researchers are striving to develop a method that reduces graft-vs-host disease (GVHD), lowers nonrelapse mortality, and increases relapse-free survival (RFS) in patients with hematologic malignancies.

While posttransplant cyclophosphamide (PTCy) is a common GVHD prophylaxis, it has been linked to increased hospitalization, nonrelapse mortality, and relapse. Orca-T, a novel cell therapy under investigation, leverages regulatory T cells from allogeneic donors to control GVHD.

A retrospective study was conducted to assess the relative efficacy of these 2 treatment regimens. The researchers compared Orca-T with PTCy-based HCT using data from existing studies that involved similar patient populations. The findings revealed that Orca-T resulted in superior outcomes compared with PTCy-based HCT, including lower rates of chronic GVHD, lower nonrelapse mortality at 1 year, and higher RFS and overall survival (OS) at 1 and 2 years.

Based on this analysis, Orca-T has the potential to improve post-HCT outcomes as compared with PTCy-based HCT for patients with acute leukemia and myelodysplastic syndrome. The positive impact on RFS, nonrelapse mortality, and OS, alongside reduced GVHD with Orca-T, underscores the significance of identifying treatment approaches that can bring about positive changes across all key transplant outcomes. Currently, a randomized phase 3 registrational trial (NCT05316701) is underway to confirm these findings.

In an interview with Targeted Oncology^TM, Alexandra Gomez Arteaga, MD, hematologist/oncologist in the bone marrow transplant and cellular therapy program at Weill Cornell Medicine in New York, New York, further discussed these findings.

Alexandra Gomez Arteaga, MD

Targeted Oncology: What was the rationale behind this study?

Gomez Arteaga: Our field in allogeneic stem cell transplantation is changing, and we now have new ways of doing GVHD prophylaxis. The posttransplant cyclophosphamide studies and the platform have shown significant reduction in chronic GVHD. There might be other ways that we can improve outcomes by reducing other important things such as toxicities and relapse. Orca-T is a high precision immunotherapy that is a more organized fashion to create immune reconstitution. Based on the like new changes in organ posttransplant cyclophosphamide, we wanted to compare Orca-T [with] posttransplant cyclophosphamide.

What is Orca-T?

In allografts, there are over 50 cell types that are infused together, and we have no control over how these cells interact for engraftment. Orca-T immune reconstitution, on the other hand, is the high-precision immunotherapy where the cells are in manufacture and divided into 3 main components. The first component is hematopoietic stem cells. The second component is highly purified T regulatory cells. The third component is the conventional cells. With this high precision immunotherapy, we can give the patient the exact number of cells at the exact time. On day 0, the patients get the stem cells from the T regulatory cells and this the regulatory cells are going do an optimal immunomodulatory environment so that there's less GVHD. There is more organization of how the immune reconstitution happens.

What unmet needs exist in this space?

We feel we have done many great things, but we still have to figure out what is the best way to do GVHD prophylaxis that does not only reduce GVHD but also decreases risk of infections and improving immune reconstitution. This is why we still need to figure out a new alternative way either to modify PTCy to decrease the infection risk and improve the immune reconstitution or also look for alternative donor graft manipulation.

What were the goals of this analysis?

Our study [was] a retrospective cohort study. We wanted to do an initial look to see how the Orca-T patients treated in the phase 1b study compared to the PTCy data right now that is published. It is very heterogeneous. There are a lot of studies that are done with bone marrow transplant primary grafts. There are some studies that use triple immunosuppression [and] other studies use only PTCy. We wanted to try to limit the heterogeneity in trying to see how does Orca-T look against PTCy.

We created a retrospective cohort study looking at patients transplanted with Orca-T in a phase 1b study and then compare them to the PTCy arm from a publicly available data set that included patients transplanted with matched unrelated donors and PTCy unmotivated conditioning.

Can you summarize your findings?

The findings of this retrospective analysis showed that Orca-T compared [with] PTCy may not only be important to reducing chronic graft-vs-host disease, but it might also be important in improving other important outcomes such as relapse-free survival, nonrelapse mortality, and overall survival. It highlights that as a field, we have to do better in trying to improve our GVHD prophylaxis methods so that we have a better reduction of toxicities.

What would be your takeaways be for the practicing oncologist?

I think the field is moving. I think that now that we have PTCy…we need to make sure we redo those adjustments based on the patient population, we need to make sure we know how to manage…infections, and we need to make sure that we manage organ toxicities. For this new platform, Orca-T, I think it is an exciting way to look at the field in terms of donor engineering, so that we have more control of how the immune reconstitution of the patients is.

REFERENCE:

Gomez-Arteaga A, Oliai C, Pantin J, et al. A retrospective analysis comparing Orca-T to post-transplant cyclophosphamide based allogeneic hematopoietic cell transplant in patients with matched unrelated donors receiving myeloablative conditioning. Presented at: 2024 Transplantation and Cellular Therapy Tandem Meetings; February 21-24, 2024; San Antonio, TX. Abstract 59.