Post-Transplant Cyclophosphamide Improves Survival in HLA-DPB1 Mismatched Unrelated Donor Allogeneic Transplantation

HLA-DPB1 mismatching is common in unrelated donor (URD) hematopoietic cell transplantation (HCT) and increases graft-versus-host disease (GVHD) when using methotrexate and tacrolimus (MTX/Tac)-based GVHD prophylaxis. Historically, national and international guidelines recommended prioritizing HLA-DPB1 matching in URD selection. The impact of HLA-DPB1 matching in URD HCT when using post-transplantation cyclophosphamide (PTCy) has been understudied. Our primary endpoint was the association of GVHD-prophylaxis strategy with overall survival (OS) after T cell-replete 12/12 HLA-matched or HLA-DPB1 permissive or non-permissive (NP) mismatch (MM) (defined by the T-cell-epitope groups model) URD HCT. GVHD-free, relapse-free survival (GRFS) was our key secondary endpoint. This was a retrospective cohort study using the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Recipients underwent a first HCT from 2015-2020 for acute leukemia or myelodysplastic syndrome using either HLA-DPB1 NP MM (n = 329), permissive MM (n = 992), or 12/12 HLA-matched (n = 300) URD with PTCy ± mycophenolate mofetil and/or a calcineurin inhibitor, or HLA-DPB1 NP MM (n = 709), permissive MM (n = 2,395), or 12/12 HLA-matched (n = 911) URD with MTX/Tac. HLA-DPB1 NP MM HCT with MTX/Tac was associated with higher treatment-related mortality (TRM) (hazard ratio [HR]: 1.64, 1.08-2.49, P = .019), lower relapse (HR: 0.73, 0.59-0.92, P = .0073), inferior OS (HR: 1.27, 1.03 -1.57, P = .023), and worse GRFS (HR: 1.61, 1.34-1.94, P < .0001) when compared with HLA-DPB1 NP MM HCT with PTCy. Adjusted 1-yr estimates for GRFS were 54% (95% confidence interval [CI]: 49-60%) for PTCy and 40% (CI: 37-44%) for MTX/Tac. For permissive MM URD HCT, MTX/Tac was associated with inferior GRFS (HR 1.54, CI: 1.36-1.76, P < .0001) when compared with PTCy. When using PTCy, there were no significant differences in the above outcomes for HLA-DPB1 NP MM, HLA-DPB1 permissive MM, or 12/12 HLA-matched URD HCT. PTCy should be the preferred GVHD prophylaxis strategy for HLA-DPB1 MM URD HCT. Furthermore, within PTCy platforms, survival is comparable across HLA-DPB1 match and thus NP mismatching at HLA-DPB1 should not be avoided in URD selection when using PTCy.