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

Abstract

Introduction: Lactate dehydrogenase (LDH) is an intracellular enzyme the concentration of which in the serum of melanoma patients is a commonly used biomarker for detecting recurrence, monitoring the effectiveness of ongoing systemic treatment, and for determination of prognosis.

Material and methods: In this report we evaluated the clinical value of elevated LDH during adjuvant BRAF (dabrafenib) and MEK (trametinib) inhibitors in 23 patients after resection of stage III cutaneous, BRAF-mutated melanoma.

Results: The treatment was administered for one year or until disease progression or unactable toxicity. In all patients, an increase in LDH was observed during treatment, of whom 18 patients had an increase to values above the upper limit of normal, while 4 patients had an increase within normal limits. After discontinuation of dabrafenib with trametinib, a decrease in LDH levels was observed in all patients except one, in whom treatment was discontinued due to disease progression. The increase in LDH was not associated with disease progression. Hypotheses explaining the increase in LDH include, among others, the immunomodulatory effect of BRAF and MEK inhibitors and the effect of drugs in question on the MAPK pathway in wild-type BRAF cells.

Conclusions: Information on the common increase in LDH in patients undergoing adjuvant therapy with dabrafenib with trametinib will avoid additional imaging studies in many situations and may prevent unnecessary emotional stress for patients.