Nivo/ipi 2nd combo infusion. LDH question.

First, it is great to hear the LDH level came down since you started treatment. Depending on the normal reference ranges at the laboratory, 225 is right at the top of the NORMAL reference range. Here is a link to a decent reference on biomarkers since LDH is known as a nonspecific biomarker for melanoma. Which means that they do use and evidence is there in the blurb below, but there are other reasons for high levels and other disease states or conditions that cause it. https://www.ncbi.nlm.nih.gov/books/NBK481856/

You can actually click on the link to the right of the page and get a copy of the entire book, but here is a helpful blurb:

LACTATE DEHYDROGENASE
Lactate dehydrogenase (LDH, EC 1.1.1.27) is a ubiquitous enzyme catalyzing the conversion of pyruvate to lactate. This reaction is essential when oxidative phosphorylation is disrupted, for instance, in anaerobic conditions and in hypoxia (8), and the latter is quite common in fast-growing tumors with high consumption of nutrients and oxygen. In the American Joint Committee on Cancer (AJCC) staging system, serum LDH is the only serum biomarker that was accepted as a strong prognostic parameter in clinical routine for melanoma, classifying those patients with elevated serum levels in Stage IV M1C (4, 5). In the recent past, the role of LDH as a prognostic factor and as a marker for treatment response has been confirmed further. In a meta-analysis of 76 studies on the prognostic role of LDH in solid tumors, including 12 melanoma studies from 1998 to 2014, Petrelli and colleagues confirmed that high serum LDH concentration is associated with lower overall survival in melanoma patients (9). Recent studies analyzed the suitability of serum LDH as marker for outcome of advanced melanoma patients after treatment with immunomodulatory drugs. In this regard, baseline serum LDH was demonstrated to be a strong predictive factor for overall survival after ipilimumab treatment in metastatic melanoma (10). The authors further concluded that long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. An independent study showed that low baseline serum LDH is associated with favorable outcome of late-stage melanoma patients treated with ipilimumab and, therefore, confirmed that baseline serum LDH is a strong marker for prognosis in advanced melanoma (11). The suitability of serum LDH as a predictive factor was also demonstrated for therapy with further immunomodulatory drugs, anti-programmed death receptor-1 (anti-PD-1) antibodies pembrolizumab and nivolumab (12). The authors documented that anti-PD-1-treated patients with a relative reduction of serum LDH compared with their baseline LDH achieved partial remission. On the other hand, patients with an increased serum LDH level compared with the baseline LDH showed progressive disease. They conclude that serum LDH is a useful marker not only at baseline but also during treatment in patients treated with anti-PD-1 antibodies in advanced melanoma. Despite many promising results, there are also some limitations in measuring LDH as a melanoma biomarker. First of all, LDH is not an actively secreted enzyme. Thus, LDH is only released through cell damage and cell death, which occur more frequently in malignant neoplasms. However, there are also false-positive values through hemolysis; hepatocellular injuries like hepatitis, myocardial infarction, and muscle diseases; and other infectious diseases with high amounts of necrotic cells (4). Moreover, LDH is nonspecific for melanoma and elevated levels are also found in many other benign and malignant diseases.