Clinical Evaluation of TMLI and PTCy in MRD-Negative AML Transplant

Anthony S. Stein, MD, professor and co-director of the acute leukemia program at City of Hope, provides a brief overview of a study presented at the 2025 Tandem Meetings (NCT03467386) which evaluated the combination of total marrow and lymphoid irradiation (TMLI) 20 Gy and post-transplant cyclophosphamide (PTCy) when given to patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation (HCT).

“[T]he 2 major causes of failure in the transplant setting are basically relapse and chronic graft-vs-host disease. In this study, we devised a plan to address both issues. One was to add PTCy, given on days 3 and 4, to try and limit the incidence of chronic graft-vs-host disease [GVHD]. However, by adding this extra immunosuppression and decreasing the risk of GVHD, there is a potential for increased relapse,” explains Stein.

In the trial, 34 patients between the ages of 18 and 60 who were in first or second complete remission (CR), were minimal residual disease (MRD)-negative, and had matched donors were included. Investigators delivered TMLI at a dose of 20 Gy to disease sites, capped at 12 Gy for brain and liver, and spared other organs (2.6 Gy to 10.4 Gy). PTCy was given to patients on days 3 and 4. This was followed by tacrolimus and was tapered from day 90 if no GVHD occurred.

“[T]he goal of this study was basically to increase the conditioning radiation dose to 2000 cGy, together with post-transplant cyclophosphamide, to address both of those issues,” says Stein.

“This is for patients with AML in first and second remission. They had to be MRD-negative and have a fully matched sibling or unrelated donor. The age initially was up to 60, but then we extended it up to 65 because it was very well tolerated,” adds Stein.

REFERENCE:

Stein A, Al Malki MM, Yang D, et al. Total marrow and lymphoid irradiation in combination with post-transplant cyclophosphamide-based graft versus host disease prophylaxis confers favorable GvHD-free/relapse-free survival in patients with acute myeloid leukemia in first or second remission. Presented at the 2025 Tandem Meeting; February 12-15, 2025; Honolulu, HI. Presentation ID 145.