Bone metastasis as an independent prognostic factor for survival in patients with advanced melanoma treated with immune checkpoint blockade.

Abstract

e22045 Background: Immune checkpoint blockade (ICB) has changed the natural history advanced melanoma (AM) with response rates about 40% and overall survival in 5 years of more than 30%. Interestingly, the site of metastasis may have impact on immune response due to the quantity and quality of immune infiltrate as we have seen in patients (pts) with liver metastasis treated with ICB. We have hypothesized that bone metastasis(BM) represents an immune less responsive site of disease Methods: We conducted a retrospective observational analysis of patients with AM treated with ICB at A.C. Camargo Cancer Center (AC) in São Paulo, Brazil. We analyze the impact of BM on progression-free (PFS) and overall survival (OS) using Kaplan Meier method, log-rank test and time-dependent COX regression model. Results: We analyzed 170 pts with AM treated with anti-PD1 (79%) or anti-PD1 + anti-CTLA4 (21%) between September 2013 and December 2019. Fifty-five percent in first-line, 22.4% second-line and the remaining in third or more lines of therapy. Ninety- four were male (55.3%), median age of 60.5 years (24.8 to 88.3) and 61 (35.9%) pts had BRAF mutation. Among stage IV patients (94%), 52 (32.4%) were M1c, 36 (22.4%) M1d and 46 (27%) had elevated LDH. Forty-two (26%) pts had BM. The overall response rate was 30.9% for pts with BM compared to 57.7% for pts without BM (p:0.004). In a median follow-up of 23.6 months (95% CI: 18.0-29.1), the median PFS and OS for pts with and without BM were 3.8 x 18.8 months (p 0.005) and 19.4months x not achieved (p 0.001), respectively. The 24-month analysis shows an overall survival rate of 38% for patients with BM compared to 62% for the rest of the cohort population. In a multivariate analysis for overall survival, acral melanoma, elevated LDH, ECOG performance status of 1 or 2 and BM were independent adverse prognostic factors (bone metastasis - HR: 2.3; 95%CI: 1.18-4.1; p:0.013). Conclusions: In this analysis, the presence of bone disease seems to be a worse independent prognostic factor for survival. A hypothesis would be the unfavorable bone microenvironment for the action of the immunotherapy.