702P - Characterization of germline HLA genotypes in patients (pts) with solid tumors treated with immunotherapy

Background

Human leukocyte antigens (HLAs) are expressed in a variety of cells, including cancer cells and immune cells. Recent studies have shown that germline HLA gene zygosity, supertype and individual HLA genotypes may be associated with immunotherapy (IO) outcomes. We aimed to evaluate whether germline HLA-A gene haplotype and zygosity is associated with response to IO.

Methods

Pts enrolled in phase 1 clinical trials in the Vall d´Hebron Institute of Oncology Early Drug Development Unit with available HLA-A testing were reviewed. Median progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

Results

From 2021 to 2023 a total of 247 eligible pts were reviewed. Median age was 59y, 63% female, main types of tumor with positive HLA biomarker were colorectal/anal cancer 19% (47pts), gynecological tumors 14%(34pts); and breast cancer 14% (34pts). Alleles present at >5% samples: 02:01:01 25%, 01:01:01 11%, 03:01:01 11%, 24:02:01 9%, 29:02:01 8%. Twenty-five (10.20%) pts presented HLA-A homozygosis. Homozygosis occurred in the most common haplotypes: 02:01:01 (14pts), 01:01:01 (2pts), 03:01:01 (4pts%), 24:02:01 (2pts%) and 29:02:01 (2pts). Eighty-five (34.5%) pts received IO; main types of tumors that received IO were genitourinary tumors 67% (10pts), gynecological tumors 45% (16pts) and colorectal/anal tumors 27% (13pts). Pts treated with anti-PD1 were 17 (20%), anti-PDL1 17 (20%) and other combinations 20 (24%). Twelve patients (17%) had PR, and thirty eight (45%) SD. Overal PFS and OS was 6.1 months and 29.6 months respectively. Presence of 03:01:01 was associated with a higher likelihood of response. Six pts with HLA homozygosis received inmunotherapy, all of them achieved SD as best response (NS).

Conclusions

Prevalence of HLA 02:01:01 in our population is significantly lower than reported in other populations. Presence of Homozygoses was not significantly associated with lack of response to inmunotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This research has been funded by CaixaResearch Advanced Oncology Research Program supported by Fundació La Caixa, by the Comprehensive Program of Cancer Immunotherapy & Immunology II (CAIMI-II) supported by the BBVA Foundation (grant 53/2021).

Disclosure

All authors have declared no conflicts of interest.