HLA Class I Genotype Is Associated with Relapse Risk after Allogeneic Stem Cell Transplantation for NPM1-Mutated Acute Myeloid Leukemia

Rupa Narayan, Abhishek Niroula, Tao Wang, Michelle Kuxhausen, Meilun He, Everett Meyer, Yi Bin Chen, Vijaya Raj Bhatt, Amer Beitinjaneh, Taiga Nishihori, Akshay Sharma, Valerie I. Brown, Malek Kamoun, Miguel A. Diaz, Muhammad Bilal Abid, Medhat Askar, Christopher G. Kanakry, Loren Gragert, Yung Tsi Bolon, Steven G.E. MarshShahinaz M. Gadalla, Sophie Paczesny, Stephen Spellman, Stephanie J. Lee

Research output: Contribution to journalArticlepeer-review

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Abstract

Mutation-bearing peptide ligands from mutated nucleophosmin-1 (NPM1) protein have been empirically found to be presented by HLA class I in acute myeloid leukemia (AML). We hypothesized that HLA genotype may impact allogeneic hematopoietic stem cell transplantation (allo-HCT) outcomes in NPM1-mutated AML owing to differences in antigen presentation. We evaluated the effect of the variable of predicted strong binding to mutated NPM1 peptides using HLA class I genotypes from matched donor-recipient pairs on transplant recipients’ overall survival (OS) and disease-free survival (DFS) as part of the primary objectives and cumulative incidence of relapse and nonrelapse mortality (NRM) as part of secondary objectives. Baseline and outcome data reported to the Center for International Blood and Marrow Transplant Research from a study cohort of adult patients (n = 1020) with NPM1-mutated de novo AML in first (71%) or second (29%) complete remission undergoing 8/8 matched related (18%) or matched unrelated (82%) allo-HCT were analyzed retrospectively. Class I alleles from donor-recipient pairs were analyzed for predicted strong HLA binding to mutated NPM1 using netMHCpan 4.0. A total of 429 (42%) donor-recipient pairs were classified as having predicted strong-binding HLA alleles (SBHAs) to mutated NPM1. In multivariable analyses adjusting for clinical covariates, the presence of predicted SBHAs was associated with a lower risk of relapse (hazard ratio [HR],.72; 95% confidence interval [CI],.55 to.94; P =.015). OS (HR,.81; 95% CI,.67 to.98; P =.028) and DFS (HR,.84; 95% CI,.69 to 1.01; P =.070) showed a suggestion of better outcomes if predicted SBHAs were present but did not meet the prespecified P value of <.025. NRM did not differ (HR, 1.04; P =.740). These hypothesis-generating data support further exploration of HLA genotype-neoantigen interactions in the allo-HCT context.

Original languageEnglish (US)
Pages (from-to)452.e1-452.e11
JournalTransplantation and Cellular Therapy
Volume29
Issue number7
DOIs
StatePublished - Jul 2023

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Molecular Medicine
  • Hematology
  • Cell Biology
  • Transplantation

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