Impact of modern systemic therapies and clinical markers on treatment outcome for metastatic melanoma in a real-world setting.

Background: The survival in metastatic melanoma has dramatically improved after the introduction of immune checkpoint- (ICIs) and MAPKinase inhibitors (MAPKis).

Objective: Our aim was to describe therapy response and survival in a real-world population as well as to assess the associations between clinical variables and therapy outcome for patients with metastatic melanoma receiving first-line ICIs or MAPKis.

Methods: A total of 252 patients with metastatic (stage IV) melanoma were prospectively followed between 1 January 2010 and 3 December 2017 with follow-up until 31 March 2019, at the Karolinska University Hospital, Sweden. Hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were analysed with Cox regression, and logistic regression was used to estimate odds ratios (ORs) for therapy response.

Results: Patients receiving ICIs (n = 138) experienced longer PFS compared to patients that received MAPKis (n = 114; median PFS for ICIs was 6.8 months, and median PFS for MAPKis was 5.3 months). In the multivariable analyses of clinical markers, increasing M-stage (OR 0.65; 95% CI 0.45-0.94; P = 0.022) and male sex (OR 0.41; 95% CI 0.19-0.90; P = 0.027) were significantly associated with lower response to ICIs. Lower baseline albumin levels (OR 0.90; 95% CI 0.83-0.98; P = 0.019) and male sex (OR 0.33; 95% CI 0.12-0.93; P = 0.036) were related with lower response to MAPKis. For ICIs, increasing M-stage (HR 1.34; 95% CI 1.07-1.68; P = 0.010), increasing LDH (HR 1.73; 95% CI 1.19-2.50; P = 0.004) and decreasing albumin (HR 1.06; 95% CI 1.01-1.10; P = 0.011) were significantly associated lower PFS in the adjusted model. The corresponding markers for MAPKis were increasing LDH (HR 1.44; 95% CI 1.08-1.92; P = 0.013) and decreasing albumin (HR 1.05; 95% CI 1.02-1.09; P = 0.005) for PFS.

Conclusion: ICIs and MAPKis were effective in this real-world population, and we could confirm the importance of previously reported clinical prognostic markers. Albumin values may be associated with therapy outcome but need further validation.