LDH Isotyping for Checkpoint Inhibitor Response Prediction in Patients with Metastatic Melanoma

Abstract

Serum lactate dehydrogenase (LDH) levels are inversely related with response to immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma. LDH is a key regulator of glycolysis, a pathway known to be upregulated in malignant tumors and to negatively affect antitumor immunity. We hypothesized that LDH isotype distribution in peripheral blood better reflects tumor glycolytic activity than total LDH levels and might therefore contribute to immunotherapy response prediction. LDH isotyping was performed in blood of 40 patients with metastatic melanoma and elevated LDH levels, of which 22 were treated with ipilimumab plus nivolumab. LDH-1 levels were decreased in 57.5% of patients. The percentage of LDH-2, -3 and -4, on the other hand, was elevated in 35%, 67.5% and 37.5% of patients, respectively. There was no difference in LDH isotype distribution between patients with versus patients without clinical benefit of ICIs, except for a numerically lower percentage of LDH-1 in patients without clinical benefit (median 13.3% vs. 17.6%, p = 0.1295). The percentage of LDH-1 correlated with total LDH levels and tumor burden and is therefore not likely to have strong, independent predictive value for response to ICIs. In conclusion, LDH isotyping does not contribute to ICI response prediction in melanoma patients with elevated LDH levels.