Calcineurin Inhibitor-Free Graft-Versus-Host Disease (GVHD) Prophylaxis in Hematopoietic Cell Transplantation (HCT) with Myeloablative Conditioning Regimens (MAC) and HLA-Matched Donors: Long Term Follow up of BMT CTN 1301 Progress II Trial

Introduction The BMT CTN 1301 trial evaluated the role of calcineurin Inhibitor (CNI)-free approaches using T-cell depletion, either by ex vivo CD 34 selection or in vivo post-transplant cyclophosphamide (PTCy) without additional immune suppression compared to tacrolimus and methotrexate with bone marrow grafts and MAC. It demonstrated no difference in the primary composite endpoint of chronic GVHD, relapse-free survival (CRFS) and worse overall survival (OS) with CD-34 selection, despite low rates of chronic GVHD. This is an updated 5 year follow up analysis. Methods BMT CTN 1301 is a phase III trial that randomized patients aged ≤ 65 years with acute leukemia or myelodysplasia (blasts <5%) and an HLA matched related or unrelated donor to receive a CD34 selected peripheral blood stem cell (PBSC) graft without posttransplant immune suppression (IS), PTCy after a bone marrow graft (BM) without additional IS or tacrolimus/methotrexate (Tac/MTX) after BM (control). For the long-term analysis data from the BMT CTN 1301 trial was merged with data reported to the Center for International Blood and Marrow Transplant Research on outcomes after completion of the trial at 24 months. Outcomes include CRFS, OS, transplant-related mortality (TRM) and disease relapse. Analysis of these outcomes were based both on intent to treat (ITT, N=346) and as treated (AT, N=300) analysis due to differential attrition with CD34 selection (86% of patients received the assigned arm - table). Outcomes were adjusted on age, donor type, performance status, disease and disease risk. Results Rates of CRFS in ITT at 5 years were 46.9% for CD34 (hazard ratio [HR] compared to control 1.33, p=0.15), 41.5% for PTCy (HR 0.88, p=0.55) and 36.5% for control. Rates of CRFS in AT at 5 years were 50.8% for CD34 (HR 1.70, p=0.05), 44.1% for PTCy (HR 0.90, p=0.65) and 36.6% for control Corresponding rates of OS in ITT were 59% (HR 1.35, p=0.18), 69.5% (HR 0.87, p=0.58) and 65.2%. Rates of OS in AT were 60.2% (HR 1.92, p=0.03), 72.3% (HR 0.97, p=0.58) and 66.1% (Figure).TRM rates in AT at 5 years were 22.8% (HR 3.80, p<0.01), 15.7% (HR 1.73, p=0.38) and 12.1%, for CD34, PTCY and control, respectively. Corresponding rates for relapse in AT were 25.4% (HR 1.11, p=0.76), 19.8% (HR 0.62, p=0.11) and 29.3%. Conclusion Long term ITT analysis of BMT CTN 1301 no differences in CRFS and OS across the groups, the AT showed better CRFS with CD34 selection compared to control but not PTCy while worse OS due to higher TRM.