Serum 5-s-cysteinyldopa for identifying non-responders to nivolumab treatment of melanoma.

Abstract

e21068 Background: Despite considerable advances in the treatment of metastatic melanoma, reliable markers to monitor treatment response are still lacking. 5-S-cysteinyldopa (5-S-CD) is a precursor of melanin that has been established as a biomarker for melanoma progression. This study evaluated serum 5-S-CD in parallel with lactate dehydrogenase (LD) as a predictor of treatment progress in melanoma patients receiving Nivolumab (Nivo) therapy. Materials and Methods: Twenty-one patients (median age: 77 years; 10 male and 11 female) with metastatic melanoma who were treated with Nivo at Shinshu University Hospital between 2014 and 2016 were retrospectively examined. Primary lesions were in the head and neck in 5 patients, trunk and extremities in 5 patients, acral area in 5 patients, mucosa in 3 patients, and an unknown site in 3 patients. Serum 5-S-CD and LD were recorded and change ratios were calculated between the baseline and values obtained 14-90 days after the initial administration of Nivo, prior to the first imaging examination. The change ratios of each biomarker were evaluated based on the response classifications defined by the RECIST criteria (version 1.1). Results: The respective baseline median concentrations of serum 5-S-CD (normal range: 2.5–6.1 nmol/L) and LD (normal range: 120–230 IU/L) were 26.5 nmol/L and 247 IU/L in partial response (PR) patients (n = 5), 74.2 nmol/L and 428 IU/L in a stable disease (SD) patient (n = 1), and 9.9 nmol/L and 237 IU/L in progressive disease (PD) patients (n = 15). The maximum change ratios of 5-S-CD before the first imaging examination were 0.13–1.14 (median: 0.34) in PR patients and 0.30–15.38 (1.52) in PD patients, as compared with 0.73–0.98 (0.96) in PR patients and 0.63–2.23 (1.04) in PD patients for LD. The maximum change ratios of 5-S-CD were ≥1.3 in 9 of 15 (60%) PD patients but < 1.3 in all (100%) PR and SD patients. Conclusions: The maximum change ratio of serum 5-S-CD in the early phase of Nivo treatment may be a useful and more sensitive marker than that of LD to predict a non-response in metastatic melanoma.