Revised HLA-DP TCE-Core Permissiveness Model Better Defines Relapse Risk and Survival Following Haploidentical Transplant.

BACKGROUND: The presence of an HLA-DPB1 non-permissive mismatch (NPMM) by the TCE-3 model has been associated with improved survival following haploidentical donor transplantation (HIDT) utilizing post-transplant cyclophosphamide (PTCy). A revised model (TCE-core) further separates TCE-3 "group 3" alleles into "core"(C) and "non-core" (NC) alleles has been recently developed, so that a formerly permissive mismatch (PMM) resulting from "group 3" alleles in both donor and recipient are now considered a C-NPMM if one or more of those alleles is NC.

OBJECTIVE: We aimed to study the additional effect of HLA-DPB1 C-NPMM per the TCE-Core algorithm, as well as the directional vector of the mismatch, on transplant outcome following HIDT.

STUDY DESIGN: To this end, 242 consecutive HIDT recipients with ALL, AML or MDS transplanted between 2005 - 2021 (median age 51 [19,80]) were analyzed. Median follow-up was 62 [23, 199] months. Of the 136 transplants classified as PMM by TCE-3, 73 were reclassified as a C-NPMM by the TCE-Core algorithm, of which 36 were in the GVH-vector (37 were HVG-only). Given comparable survival between conventional NPMM and C-NPMM GVH/bidirectional were analyzed together (nonpermissive). HVG-only C-NPMM were combined with HLA-DPB1 matched and PMM (permissive) due to similar outcomes.

RESULTS: The presence of a TCE-Core-defined nonpermissive HLA-DP mismatch resulted in superior 5-year OS (66% vs. 47%) and DFS (60% vs. 43%). Compared to the conventional TCE-3 algorithm, TCE-Core identified a larger number of nonpermissive transplants (38% vs. 23%) and better discriminated outcomes between nonpermissive vs. permissive status (larger difference in survival outcome using TCE-Core vs. TCE-3, with OS Δ of 18.3% vs. 12.7%; DFS Δ of 16.5% vs. 8.5%). In multivariable analysis, a nonpermissive TCE-core mismatch led to improved OS (HR 0.54, p=0.003) and DFS (HR 0.62, p=0.013), due in large part to decreased relapse risk (HR 0.63, p=0.049). In contrast, NRM or GVHD outcomes were not significantly impacted.

CONCLUSION: In summary, the presence of nonpermissive TCE-Core HLA-DP mismatch strongly predicts survival following PTCy-based HIDT, due to a reduction in relapse risk without a corresponding increase in GVHD or NRM. As a donor selection tool, TCE-Core appears to better discriminate HIDT outcome while at the same time identifying a larger percentage of the potential donor pool.