Intensifying Conditioning in Older Patients and Unanswered Questions in Allogeneic Transplant

Robert Negrin, MD, asks whether lower nonrelapse mortality with the Orca-T approach could allow higher-intensity conditioning to be delivered safely to older patients. Caspian Oliai, MD, MS, suggests looking at what other than conditioning intensity drives early nonrelapse mortality; if factors such as the amount of immunosuppression and the use of a chemotherapy as graft-vs-host disease (GVHD) prophylaxis can be minimized, conditioning might be intensified in patients who otherwise could not tolerate it. With Orca-T, prophylaxis is tacrolimus alone. Rawan Faramand, MD, agrees the idea has merit and warrants evaluation. Her institution does not give myeloablative conditioning to patients older than 65 years, yet the aging population carries higher-risk disease, including TP53-mutated disease and leukemia transformed from myelodysplastic syndrome or essential thrombocythemia, so studying myeloablative conditioning with this platform in older patients who remain fit is, in her view, an important area of investigation. In closing, Dr Faramand defines success as more than survival: fewer medications, earlier discontinuation of immunosuppression, less chronic GVHD, fewer infections, and faster return to work, school, and normal quality of life. She sees the field moving from a one-size-fits-all model toward a personalized approach that accounts for patient and disease characteristics, relapse risk, conditioning, graft source, and a GVHD prophylaxis platform that reduces GVHD while preserving the graft-vs-leukemia effect. Dr Oliai emphasizes relapse rates at 2 and 3 years, noting that reaching 3 years without relapse in acute myeloid leukemia is a major milestone and that trials reporting only 1-year outcomes cannot capture chronic GVHD that emerges between years 1 and 2. Dr Faramand adds that prospective trials comparing contemporary platforms with longer follow-up are still needed. Dr Negrin thanks the panel and closes the program.