Prognostic Hematologic Biomarkers Following Immune Checkpoint Inhibition in Metastatic Uveal Melanoma

Simple Summary Uveal melanoma is a rare form of melanoma but is the most common tumor in the eye. Despite having effective treatments for the initial tumor, many patients experience the spread of their cancer to distant body sites. There is no uniform way of treating metastatic disease, but physicians often use therapies that harness the patient's immune system because these same treatments have been very effective in other types of melanoma. Not all patients respond to this therapy though, and some develop toxicity related to the treatment. The goal of this paper was to identify features or blood markers that may help determine response to treatment early. Specifically, we analyzed a molecule called lactate dehydrogenase (LDH) and the ratio of different white blood cells at the start of therapy and 2 months after treatment was started. We found that these non-invasive blood markers could be useful in determining which patients are responding to treatment. Background: There is no standardized treatment for metastatic uveal melanoma (MUM) but immune checkpoint inhibitors (ICI) are increasingly used. While ICI has transformed the survival of metastatic cutaneous melanoma, MUM patients do not equally benefit. Factors known to affect ICI response include the hematologic markers, lactate dehydrogenase (LDH) and neutrophil:lymphocyte ratio (NLR). We evaluated the prognostic value of LDH and NLR at the start of ICI and on treatment in MUM. Methods: MUM patients were treated between August 2006 and May 2022 with combination ipilimumab/nivolumab or ipilimumab/nivolumab/pembrolizumab single-agent therapy. Univariable (UVA) and multivariable (MVA) analyses were used to assess the prognostic value of predefined baseline factors on progression-free (PFS) and overall survival (OS). Results: In forty-six patients with MUM treated with ICI, elevated baseline and on-treatment LDH was prognostic for OS (start of ICI, HR (95% CI): 3.6 (1.9-7.0), p < 0.01; on-treatment, HR (95% CI): 3.7 (1.6-8.8), p < 0.01) and PFS (start of ICI, (HR (95% CI): 2.8 (1.5-5.4), p < 0.0001); on-treatment LDH (HR (95% CI): 2.2 (1.1-4.3), p < 0.01). On-treatment NLR was prognostic for PFS (HR (95% CI): 1.9 (1.0-3.9), p < 0.01). On-treatment LDH remained an important contributor to survival on MVA (OS: HR (95% CI): 1.001 (1.00-1.002), p < 0.05); PFS: HR (95% CI): 1.001 (1.00-1.002), p < 0.01). Conclusions: This study demonstrates that LDH and NLR could be useful in the prognostication of MUM patients treated with ICI. Additional studies are needed to confirm the importance of these and other prognostic biomarkers.

Automated summary

Uveal melanoma is a rare but common eye tumor with no standardized treatment for metastatic disease. This study suggests that lactate dehydrogenase and white blood cell ratio could be useful blood markers for determining treatment response.