No Impact of NRAS Mutation on Features of Primary and Metastatic Melanoma or on Outcomes of Checkpoint Inhibitor Immunotherapy: An Italian Melanoma Intergroup (IMI) Study
Michele Guida, Nicola Bartolomeo, Pietro Quaglino, Gabriele Madonna, Jacopo Pigozzo, Anna Di Giacomo, Alessandro Marco Minisini, Marco Tucci, Francesco Spagnolo, Marcella Occelli, Laura Ridolfi, Paola Queirolo, Ivana De Risi, Davide Quaresmini, Elisabetta Gambale, Vanna Chiarion‐Sileni, Paolo A. Ascierto, Lucia Stigliano, Sabino Strippoli, on behalf of the Italian Melanoma Intergroup (IMI) Study
Abstract
Aims: It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt. We compared the two cohorts regarding the characteristics of primary and metastatic disease, disease-free interval (DFI) and outcome to CII. No substantial differences were observed between the two groups at melanoma onset, except for a more frequent ulceration in the wt/wt group (p = 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95% CI, 7–18) versus 9 months (95% CI, 6–16) and 32 (95% CI, 23–49) versus 27 months (95% CI, 16–35), respectively). Irrespectively of mutational status, a longer OS was significantly associated with normal LDH, <3 metastatic sites, lower white blood cell and platelet count, lower neutrophil-to-lymphocyte (N/L) ratio. Our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant MM.