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

Narayan R, Niroula A, Wang T, Kuxhausen M, He M, Meyer E, Chen YB, Bhatt VR, Beitinjaneh A, Nishihori T, Sharma A, Brown VI, Kamoun M, Diaz MA, Abid MB, Askar M, Kanakry CG, Gragert L, Bolon YT, Marsh SGE, Gadalla SM, Paczesny S, Spellman S, Lee SJ

Transplant Cell Ther 29 (7) 452.e1-452.e11 [2023-07-00; online 2023-03-29]

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.

Abhishek Niroula

DDLS Fellow

PubMed 36997024

DOI 10.1016/j.jtct.2023.03.027

Crossref 10.1016/j.jtct.2023.03.027

mid: NIHMS1899184
pmc: PMC10330307
pii: S2666-6367(23)01204-6

Publications 9.5.0