High immunopeptidome divergence in single class I HLA mismatches between the donor and recipient of a hematopoietic cell transplant (HCT) predicted worse survival, according to a retrospective study published in the Journal of Clinical Oncology.
“We hypothesized that immunopeptidome divergence, as predicted by differences in the peptide-binding motifs (PBM) of mismatched HLA class I alleles, might also inform clinical outcomes after 9 of 10 HLA-matched unrelated donor HCT (UD-HCT),” the authors wrote in their report.
The retrospective study evaluated data from 2391 and 14,426 patients who underwent single class I HLA-mismatched or fully HLA-matched, respectively, UD-HCT between 2008 and 2018. Immunopeptidome divergence was determined using PBM as a surrogate marker. The primary endpoint was overall survival (OS).
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PBM mismatches, regardless of whether they were bidirectional or unidirectional in the graft-versus-host (GVH) direction (PBM-GVH mismatch), were associated with significantly shorter OS compared with full matches (hazard ratio [HR], 1.48; 95% CI, 1.33-1.64; P <.0001). In contrast, unidirectional PBM host-versus-graft mismatches demonstrated similar OS outcomes as PBM-GVH matches (HR, 1.13; 95% CI, 0.98-1.30; P =.1017).
There was an increased risk for transplant-related mortality for both PBM-GVH match (HR, 1.22; 95% CI, 1.06-1.41; P =.0047) and PBM-GVH mismatch (HR, 1.56; 95% CI, 1.37-1.78; P <.0001) compared with fully matched UD-HCTs.
PBM-GVH mismatch UD-HCTs were also significantly associated with a higher risk for acute GVH disease that was grade 2-4 (HR, 1.29; 95% CI, 1.16-1.43; P <.0001) or grade 3-4 (HR, 1.77; 95% CI, 1.54-2.04; P <.0001) compared with fully matched UD-HCTs. A similar association was observed for chronic GVH disease (HR, 1.31; 95% CI, 1.18-1.46; P <.0001).
There was no association between PBM match or mismatch and fully matched UD-HCTs and relapse. The authors concluded that “PBM-GVH mismatches inform mortality risks after single class I HLA-mismatched UD-HCT, suggesting that prospective consideration of directional PBM-matching status might improve outcome.”
Disclosures: This study was supported by multiple biotech, pharmaceutical, and device companies. Please see the original reference for a full list of disclosures.
Reference
Crivello P, Arrieta-Bolanos E, He M, et al. Impact of the HLA immunopeptidome on survival of leukemia patients after unrelated donor transplantation. J Clin Oncol. Published online January 20, 2023. doi: 10.1200/JCO.22.01229
