Clinical determinants of long-term survival in metastatic uveal melanoma

Abstract

This study aimed to identify prognostic factors in patients with metastatic uveal melanoma (UM) that were associated with long-term survival in a real-world setting. A total of 94 patients with metastatic UM were included from German skin cancer centers and the German national skin cancer registry (ADOReg). Data were analyzed for the response to treatment, progression-free survival, and overall survival (OS). Prognostic factors were explored with univariate Cox regression, log-rank, and χ2-tests. Identified factors were subsequently validated after the population was divided into two cohorts of short-term survival (< 2 years OS, cohort A, n = 50) and long-term survival (> 2 years OS, cohort B, n = 44). A poor ECOG performance status (hazard ratio [HR] 2.0, 95% confidence interval [CI] 1.0–3.9) and elevated serum LDH (HR 2.0, 95% CI 1.0–3.8) were associated with a poor OS, whereas a good response to immune checkpoint blockade (ICB, p < 0.001), radiation therapy (p < 0.001), or liver-directed treatments (p = 0.01) were associated with a prolonged OS. Long-term survivors (cohort B) showed a higher median number of organs affected by metastasis (p < 0.001), while patients with liver metastases only were more common in cohort A (40% vs. 9%; p = 0.002). A partial response to ICB was observed in 16% (12/73), being 21% (8/38) for combined ICB, 17% (1/6) for single CTLA4 inhibition, and 10% (3/29) for single PD1 inhibition. One complete response occurred in cohort B with combined ICB. We conclude that the response to ICB and the presence of extrahepatic disease were favorable prognostic factors for long-term survival.

Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Re-Induction following Resistance or Toxicity

“…The OS of 11.9 months is lower compared to previous retrospective studies, in which OS was 16 and 22.3 months in a real-world setting when treatment with ICB was available [4,5]. These data suggested that the prognosis of patients with advanced UM has improved due to the availability and more frequent use of ICB [4,5,9,13]. The lower OS in this collective is probably due to a relatively delayed treatment start, in particular in cohort A as the re-induction with ICB preferably occurred in later treatment lines.…”

“…We detected a median OS of 11.9 months (95% CI 9.4-15.6) and a median PFS of 2.5 months (95% CI 2.2-3) to any ICB for the entire cohort. The OS of 11.9 months is lower compared to previous retrospective studies, in which OS was 16 and 22.3 months in a real-world setting when treatment with ICB was available [4,5]. These data suggested that the prognosis of patients with advanced UM has improved due to the availability and more frequent use of ICB [4,5,9,13].…”

“…However, many values were missing. The median number of affected organ systems was higher in cohort A, which was previously a favorable prognostic factor associated with long-term survival and treatment response to ICB [4]. This imbalance may act as a confounding factor regarding OS.…”

“…The era of immune checkpoint blockade (ICB) with nivolumab and pembrolizumab (anti-PD-1) alone or in combination with ipilimumab (anti-CTLA-4) has led to significant survival benefits in patients with cutaneous melanoma (CM). However, the response rates to ICB in UM were consistently low, and potentially severe immune-related side effects may occur [4][5][6]. The objective response rate (ORR) of combined ICB lies within the range of 11.5-18% in two prospective phase II trials [7][8][9].…”

Combination of Immune Checkpoint Inhibitors and Liver-Specific Therapies in Liver-Metastatic Uveal Melanoma: Can We Thus Overcome Its High Resistance?

“…A prognostic score for patients with MUM, including the variables time to metastatic diagnosis, presence of bone metastases, and LDH, was recently developed [ 41 , 42 , 43 ]. Based on the results of our analysis, the parameters age (cut-off: ≥55 years), as well as LDH, S100, and NLR (cut-off: 3.5), should be considered in case of prognosis assessment.…”