Scordo on Model-Based ATG Dosing in Allo-HCT

While ex vivo CD34-selected allogeneic hematopoietic stem cell transplants (allo-HCT) are associated with improved chronic graft-vs-host disease-free relapse-free survival, delayed immune reconstitution and higher non-relapse mortality are possible.

A phase 2 study (NCT04872595) sought to improve immune recovery after ex vivo CD34-selected allo-HCT by using a personalized dosing strategy for the drug antithymocyte globulin (ATG). Previous research showed high ATG exposure after traditional dosing led to delayed immune recovery and increased mortality.

Michael Scordo, MD, medical oncologist, bone marrow transplant specialist, and cellular therapist at Memorial Sloan Kettering Cancer Center in New York, NY, presented findings from the study as a late-breaking abstract at the 2024 Transplantation and Cellular Therapy Tandem Meetings.

A total of 59 patients with blood cancers received model-based ATG targeting a lower exposure level compared to traditional methods. The primary goal was to achieve better immune recovery (measured by CD4-positive T-cell levels) in more patients.

Among 54 evaluable patients, 69% achieved the desired immune recovery level by day 100, meeting the study's primary end point. This improvement in immune recovery came with low rates of death not related to the cancer (9%) and high overall survival (86%) at 2 years. These results suggest that previous reports of high mortality in this type of transplant might have been due to high ATG exposure, which can be mitigated by the new dosing strategy.

While the study was conducted at a single center and long-term follow-up is ongoing, the findings suggest that model-based ATG dosing in ex vivo CD34-selected allo-HCT leads to better immune recovery and potentially improved survival compared to traditional dosing strategies. This personalized approach might help address a critical challenge in this type of transplant.

Here, Scordo disscusses the implications of these findings for a community oncologist.

Transcription:

0:05 | To community oncologists, I would say that for patients with myeloid malignancies, there are many different types of transplants that can be done safely and effectively. The appropriate choice of a platform really depends on many factors. And we can improve on all of these platforms individually, including [post-transplant cyclophosphamide], ex vivo CD34 selection, I look at this as a method of just improving on what we've already shown to be an effective platform. And again, being able to use dose-intensive chemotherapy or total body radiation to achieve maximal disease control but making the platform safe and tolerable.