77P - Impact of germline HLA genotypes on clinical outcomes in patients (pts) with solid tumors treated with immunotherapy

Background

Germline genetic factors can potentially be good biomarkers since they influence immune traits in many diseases. Human leukocyte antigens (HLAs) are expressed in a variety of cells, including cancer cells and immune cells, whereas HLA molecules play critical roles in triggering cytotoxic T lymphocytes (CTL)-mediated tumor cell killing, T cell priming, and clonal expansion. Recent studies have shown that germline HLA gene zygosity, supertype, evolutional divergence, and individual HLA genotypes are associated with the prognosis ofcheckpoint blockade immunotherapy. The purpose of our work was to evaluate biomarker inclusion and response to immunotherapy in pts who underwent germline HLA analysis in Vall d´Hebron Institute of Oncology (VHIO)-Drug Development Unit.

Methods

Pts with solid tumors included in early clinical trials who require germline HLA testing in VHIO's Early Drug Development Unit were included in the analysis from December 2021 to November 2022.

Results

A total of 177 eligible pts. Median age was 59y, main tumor types were colorectal cancer(18%), ovarian cancer(15.8%), breast cancer(12.42%) and pancreatic cancer(12.42%). Most pts(42.93%) were included based on a positive biomarker (21.46% HLA-A01:01, 42.93% HLA-A02:01 and 12.42% HLA-A03:01). Pts treated with anti-PDL1 18 pts(10.17%), anti-PD1 were 14pts(7.90%), anti-PD1 + anti-PDL1 1pts (0.56%), anti-PD1 + other study treatment 19pts(10.73%), anti-PDL1 + other study treatment 4pts(2.26%), other immunotherapy treatment 7pts(3.95%). Association between HLA A02:01 and response to immunotherapy was found significant (p-value 0.0156). The response obtained by CT scan of the pts included in the analysis was progression disease (16pts, 9.03%), stable disease (31pts, 17.51%), partial response (15pts, 8.47%).

Conclusions

High expression of germline HLA-A02:01 genotype is associated with prognosis and response in patients(pts) with solid tumors treated with immunotherapy. HLA-A02:01 genotype potentially be good biomarkers since they influence immune traits in many diseases.

Clinical trial identification

Editorial acknowledgement

Cellex Foundation Institutional grant: research facilities and equipment La Caixa Foundation Institutional grant: LCF/PR/CEO7/50610001

Legal entity responsible for the study

The authors.

Funding

Cellex Foundation Institutional grant: research facilities and equipment La Caixa Foundation Institutional grant: LCF/PR/CEO7/50610001.

Disclosure

All authors have declared no conflicts of interest.