Treating CMM patients with ICI have significantly increased PFS and overall survival (OS) for this patient population. In order to further improve ICI efficacy we need to identify predictive biomarkers to foresee which patient would benefit from treatment. Extensive research is being performed globally but with very little focus on host genotype variations. The aim of this study was to identify host genetic markers that can predict treatment outcome in patients with metastatic CMM.
We have genotyped 49 patients with metastatic CMM treated with ICI at Karolinska University Hospital in Sweden. Blood samples were collected before treatment start. As platform we have used the Axiom Precision Medicine Research Arrays (Affymetrix ®). We have conducted genome-wide and targeted analysis of approximately 488,000 and 4000 single nucleotide variants respectively, using Partek Genomic Suite Software®.
49 patients were included between July 2015 and August 2017, 22 females and 27 males. The median age was 68 years old (range 31 – 84). All patients had metastatic disease (33 M1C, 5 M1B, 11 M1A). ICI was first line treatment in most of the patients (n:40). Patients were treated with either nivolumab or pembrolizumab. Twenty-eight patients achieved disease control (with 8 complete responses) whereas 19 had progressive disease. Eleven patients were still responding at the cut-off date in 2018 November 30th, 1 missed follow-up and 2 were not included in the response analysis due to premature death. Median PFS was 6,9 months (range 0 – 40 months). The median OS was 19 months (range 0 – 40 months, 22 patients still alive at cut-off). We have in the targeted analysis identified one candidate significantly associated with both response and PFS. We are expanding the cohort and genotyping 40 additional patients.
Host genotype variations could identify novel predictive biomarkers candidates to ICI. Validation of our results with a bigger cohort is warranted.
Karolinska Institute.
Cancer Research Funds of Radiumhemmet, The Swedish Cancer Society and Knut and Alice Wallenberg Foundation.
All authors have declared no conflicts of interest.