NF1 Mutated Metastatic Melanoma and Response to Immune Checkpoint Inhibitor Therapy: A Retrospective Analysis

1.1. Background: Based on molecular profiling, malignant melanoma is classified in four different groups. NF1-mutated tumors are a small subgroup occurring with a frequency of 13% of all malignant melanomas, usually harboring a high tumor mutational burden (TMB). Considering TMB as being a prerequisite for the effectiveness of immune checkpoint inhibitor therapy, we were wondering if this rare subtype is associated with a higher response rate to immunotherapy than it is known for the general melanoma population. 1.2. Methods: We analyzed a small cohort of 14 NF1 mutated metastatic melanoma patients and retrospectively assessed the response rate (RR) according to RECIST 1.1, Progression Free Survival (PFS) and Overall Survival (OS). We compared our results with outcome data reported in several clinical trials with immune checkpoint inhibitors. 1.3. Results: For our cohort, we noticed an objective response rate of 64%, which is higher than the response rate generally reported for anti-PD1 based therapy in a population of melanoma patients. The PFS rate at twelve months was 62%, next to an OS rate at twelve months of approximately 84%. Additional mutations co-occur in NF1-mutated patients. Although we did not find an association between the number of additional mutations and response in general, we did notice a significant correlation between mutations in TERT promotor region and tumor response (p-value 0.027). 1.4. Conclusion: Despite the small patient group, we observed a higher response rate for NF1 mutated metastatic melanoma patients treated with immunotherapy. In addition, a significant correlation between response rate and the presence of hTERT promotor mutations was observed