Abstract
Introduction: Maximal heterozygosity on the human leukocyte antigen (HLA) loci has been found to be associated with improved survival and development of immune-related adverse events (irAEs) among NSCLC patients treated with immunotherapy. Here, we investigated the effect of germline HLA-I/-II on clinical outcomes among NSCLC patients treated with first-line pembrolizumab in combination with chemotherapy. Method: We prospectively recruited patients with NSCLC who were commencing first-line pembrolizumab in combination with chemotherapy. DNA from white blood cells was used for high-resolution HLA-I/II typing. Results: Of the 65 patients recruited, 53 complied with the inclusion criteria. We did not find an association between HLA-I/-II homozygosity and clinical outcome among the studied population. However, the presence of HLA-A01 was associated with unfavourable PFS (HR = 2.32, 95%CI 1.13–4.77, p = 0.022) and worsening OS (HR = 2.86, 95%CI 1.06–7.70, p = 0.038). The presence of HLA-B27 was associated with improved PFS (HR = 0.35, 95%CI 0.18–0.71, p = 0.004) and trends toward improving OS. None of the HLA-I supertypes were associated with the development or worsening of irAEs. Conclusions: The absence of association between genomic HLA-I/-II homozygosity and clinical outcome among patients with advanced NSCLC treated with pembrolizumab in combination with chemotherapy might reflect a diminished role for HLA molecules among patients with low or no PD-L1. HLA-A01 and HLA-B27 might have a role in predicting clinical outcomes among this cohort of patients. Further studies are needed to explore biomarkers for this group of patients.
Original language | English |
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Article number | 3102 |
Journal | Cancers |
Volume | 16 |
Issue number | 17 |
DOIs | |
Publication status | Published - 7 Sept 2024 |