Elevated lactate dehydrogenase in adjuvant BRAF and MEK inhibitor therapy does not have diagnostic significance in detecting melanoma recurrence

Introduction: Lactate dehydrogenase (LDH), an enzyme found within cells, is frequently measured in the blood serum of melanoma patients as a biomarker. Its concentration is used to detect the return of the disease, to monitor how well ongoing systemic treatments are working, and to help determine the likely course of the disease.

Material and methods: In this report, the clinical significance of elevated LDH levels was assessed in 23 patients who had undergone surgery for stage III cutaneous melanoma with a BRAF mutation. These patients were receiving adjuvant treatment with BRAF (dabrafenib) and MEK (trametinib) inhibitors.

Results: The treatment was given for a period of one year or until the disease started to progress or the side effects became unmanageable. During the treatment period, an increase in LDH levels was observed in all patients. Specifically, 18 patients experienced an increase that exceeded the normal upper limit, while 4 patients showed an increase that remained within the normal range. Following the discontinuation of dabrafenib and trametinib, a reduction in LDH levels was noted in all patients except for one, whose treatment was stopped due to the progression of the disease. Notably, the increase in LDH levels during treatment was not found to be associated with disease progression. Several potential explanations for the observed increase in LDH were considered, including the immunomodulatory effect of BRAF and MEK inhibitors and the impact of these drugs on the MAPK pathway in cells that do not have the BRAF mutation (wild-type BRAF cells).

Conclusions: The finding that an increase in LDH is commonly observed in patients receiving adjuvant therapy with dabrafenib and trametinib is important. This information can help to avoid the need for additional imaging studies in many cases and may prevent unnecessary emotional distress for patients who might otherwise be concerned by elevated LDH levels during their treatment.