Promising New Therapy for Hematologic Malignancies in Young Patients

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Alice Bertaina, MD, discusses combining of T-allo10, a donor-derived cell product, with haploidentical stem cell transplants for the treatment of pediatric and young adult patients with hematologic malignancies.

While haploidentical stem cell transplantation remains a standard-of-care for treatment of hematologic malignancies, the procedure is not without its challenges. These include difficulties finding perfectly matched donors, suboptimal immune system recovery, and increased risk of complications, particularly graft-vs-host disease (GVHD). However, solutions for mitigating these challenges are on the horizon.

At the 2024 Transplantation and Cellular Therapy Tandem Meetings, Alice Bertaina, MD, professor of pediatrics and chief of the pediatric stem cell transplantation program at the Stanford School of Medicine, presented findings from a phase 1/1b study integrating a new T-cell immunotherapy known as T-allo10. T-allo10 is derived from donor cells and enriched with regulatory Tr1 cells to suppress GVHD. It also contains additional T cells crucial for fighting infections and cancer cells and aims to improve immune system recovery and reduce risks of infections and relapse without causing severe GVHD.

The study enrolled 14 pediatric and young adult patients, and 13 received the T-allo10 infusion. No dose-limiting toxicities were observed. Mild GVHD occurred in some patients, with half progressing to chronic GVHD.

Importantly, a significant portion of patients (63%) achieved successful immune system recovery compared to historical data. The T-allo10 infusion increased specific immune cells linked to reduced infections. Further, Tr1 were detected, supporting the theory of reduced GVHD risk.

This early-stage study suggests T-allo10 infusion after stem cell transplant may be a promising therapy for young patients with hematologic malignancies by improving immune system recovery and potentially reducing the risk of complications. Further research is needed to confirm these findings and explore the long-term benefits of this approach.

Transcription:

0:05 | No patients transplanted so far with this approach had transplant-related mortality, which is absolutely excellent considering the very high-risk population that we are treating in the first cohort. We even had 3 patients who received this transplant as a second transplant.

Second, in the patients treated at the intermediate and high dose of T-allo10 cells, we have a 2-year leukemia free survival and GVHD-free relapse free survival of 100%, which means that all those patients at 1 year after the transplant are alive, disease-free without having severe acute GVHD or chronic graft-vs-host disease. 

0:44 | One of our hypotheses was really the that the tier 1 enrichment of the T-allo10 cell product is the key ingredient and could have been traced and make sure that persists in the recipient. Our findings show that shortly after infusion, we have an expansion of this tier 1 population, which reached a peak between day 1 and day 7 up to 20%, but then they persist longer. In the longer follow-up, we see an actually significantly improvement in terms of CD4 immune reconstitution, which is especially into the memory compartment, but it's contributing also to the naive immune reconstitution, which is, again, a second additional step. We think that the infusion of the cells can also drive endogenous thymopoiesis.

We see a trend in improvement in terms of viral infection. In patients in cohort 2 and cohort 3 specifically, we see a reduced frequency of viral infections in comparison with historical control, especially for [cytomegalovirus] and adenovirus.

1:55 | I think that the main takeaway is that really, if we can utilize, if we can combine with a transplant a donor-derived cell product which is not going to cause graft-vs-host disease, we can quickly improve the immune reconstitution and have a much better long-term control of the disease.

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