Precision-T Data in Context and the Landscape of Emerging Transplant Strategies

Caspian Oliai, MD, MS, interprets the phase 3 Precision-T trial, which compared Orca-T with a standard allogeneic transplant using tacrolimus and methotrexate under myeloablative conditioning, as an unequivocal advantage for Orca-T over a T-cell replete graft in that setting. The more interesting and still unanswered question, in his view, is how Orca-T would perform head to head against post-transplant cyclophosphamide, particularly with reduced-intensity conditioning. No such comparison has been done; the multi-institution phase 2 SERENE-T trial is evaluating Orca-T with reduced-intensity conditioning but not against post-transplant cyclophosphamide. Cross-trial comparisons of single-institution phase 2 post-transplant cyclophosphamide data in the myeloablative setting and the randomized Orca-T data suggest nonrelapse mortality of roughly 10% or less with either approach vs a historical expectation of about 20%, with low rates of graft-vs-host disease (GVHD) and no signal of higher relapse, although longer follow-up is needed. Dr Oliai then frames the broader landscape of innovation around a question he raises with patients: how many agents does it take to reach a nonrelapse mortality near 10% with low GVHD rates. Post-transplant cyclophosphamide relies on 3 agents including a chemotherapy, abatacept-based regimens are also multiagent, and Orca-T uses single-agent tacrolimus prophylaxis. Rawan Faramand, MD, agrees, noting that many young adults prefer a single agent and that post-transplant cyclophosphamide, although transformative, carries increased infection risk and potential organ toxicity including cardiac toxicity, prompting trials that optimize its dose. Tacrolimus, methotrexate, and abatacept improved acute but not chronic GVHD, and she stresses that reducing chronic GVHD is incredibly important for patients. The faculty agree that every regimen carries its own risk that must be weighed against the goal of reducing GVHD.