Adjuvant anti-PD-1 therapy improves melanoma-specific survival in stage IIIC-IV melanoma patients with high tumor mutation burden and BRAF V600 mutation

Julia Forschner¹Julia Huynh²Christopher Schroeder³Sorin Armeanu-Ebinger³Olga Seibel-Kelemen³Axel Gschwind³Irina Bonzheim⁴Thomas K. Eigentler²Teresa Amaral¹Stephan Ossowski³Lukas Flatz¹Claus Garbe¹Andrea Forschner¹Markus Reitmajer^1*

• ¹Department of Dermatology, University Hospital Tübingen, Tübingen, Baden-Württemberg, Germany
• ²Department of Dermatology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
• ³Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
• ⁴Institute of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany

Immune checkpoint inhibitors (ICI) have significantly improved melanoma-specific survival (MSS), particularly in patients with tumors with a high tumor mutational burden (TMB) or BRAF mutation. In the adjuvant setting, ICIs significantly improve relapse-free survival (RFS), but data on MSS are still lacking. Tissue samples from 83 patients with stage IIIC/D/IV melanoma who started adjuvant ICI between March 2018 and September 2019 were examined using a 700 gene panel. TMB and BRAF V600E/K mutation status were analyzed to determine their potential influence on RFS and MSS. TMB levels ≥ 20 Var/Mb were classified as TMB high, corresponding to the top 20% TMB levels in the cohort.RFS and MSS were significantly improved in patients whose tumors had high TMB levels and BRAF V600E/K mutation (p<0.001 and p=0.002, respectively).Patients with BRAF-mutated tumors and high TMB seem to benefit particularly from adjuvant ICI.