Pre‐ and on‐treatment lactate dehydrogenase as a prognostic and predictive biomarker in advanced non–small cell lung cancer

Abstract

BACKGROUND:The survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are variable. This study investigated whether pre-and on-treatment lactate dehydrogenase (LDH) could better prognosticate and select patients for ICI therapy. METHODS: Using data from the POPLAR and OAK trials of atezolizumab versus docetaxel in previously treated advanced NSCLC, the authors assessed the prognostic and predictive value of pretreatment LDH (less than or equal to vs greater than the upper limit of normal). They further examined changes in on-treatment LDH by performing landmark analyses and estimated overall survival (OS) distributions according to the LDH level stratified by the response category (complete response [CR]/ partial response [PR] vs stable disease [SD]). They repeated pretreatment analyses in subgroups defined by the programmed death ligand 1 (PD-L1) status. RESULTS: This study included 1327 patients with available pretreatment LDH. Elevated pretreatment LDH was associated with an adverse prognosis regardless of treatment (hazard ratio [HR] for atezolizumab OS, 1.49; P = .0001; HR for docetaxel OS, 1.30; P = .004; P for treatment by LDH interaction = .28). Findings for elevated pretreatment LDH were similar for patients with positive PD-L1 expression treated with atezolizumab. Persistently elevated on-treatment LDH was associated with a 1.3-to 2.8-fold increased risk of death at weeks 6, 12, 18, and 24 regardless of treatment. Elevated LDH at 6 weeks was associated with significantly shorter OS regardless of radiological response (HR for CR/PR, 2.10; P = .04; HR for SD, 1.50; P < .01), with similar findings observed at 12 weeks. CONCLUSIONS: In previously treated advanced NSCLC, elevated pretreatment LDH is an independent adverse prognostic marker. There is no evidence that pretreatment LDH predicts ICI benefit. Persistently elevated on-treatment LDH is associated with worse OS despite radiologic response.

Prognostic value of lactate dehydrogenase in non-small cell lung cancer patients with brain metastases: a retrospective cohort study

“…In patients with advanced NSCLC treated with immune checkpoint inhibitors (ICIs), elevated pretreatment LDH is an independent marker of poor prognosis. Moreover, the continuous increase in LDH during treatment is associated with poor OS ( 27 ). In advanced NSCLC patients receiving platinum-based chemotherapy, increased LDH (≥20%) and high LDH before treatment are associated with lower OS ( 28 ).…”

Elevated preradiotherapy serum lactate dehydrogenase predicts distant metastasis for lymphoepithelial carcinoma of major salivary gland following postoperative radiotherapy

“…Lactate dehydrogenase (LDH) is an important component of cellular glycolysis, and it can be detected through routine hematological tests clinically. The elevated pretreatment serum LDH was illustrated to be a prognostic indicator for poor overall survival (OS) in the breast cancer and lung cancer 10,11 . Apart from the prognostic value in cancers, the pretreatment LDH was supported by several retrospective studies 12,13 as an effective indicator for predicting cancer progression, therapeutic response, and distant metastasis in NPC and several other solid tumors.…”

“…The elevated pretreatment serum LDH was illustrated to be a prognostic indicator for poor overall survival (OS) in the breast cancer and lung cancer. 10,11 Apart from the prognostic value in cancers, the pretreatment LDH was supported by several retrospective studies 12,13 as an effective indicator for predicting cancer progression, therapeutic response, and distant metastasis in NPC and several other solid tumors. However, the predicting role of serum LDH for cumulative incidence of DM in the LECSG was inconclusive.…”

Lactate Dehydrogenase Predicts Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

“…Lactate dehydrogenase (LDH), an end product of glycolysis, is a hydrogen transfer enzyme in many cells and organs, including the heart, lung, liver, and central nervous system [5][6][7][8]. The irregular extracellular occurrence of LDH, which can be detectable in serum to discover cell or organ injury, has been noted as a warning sign in a wide range of clinical situations, including myocardial ischemia, myocarditis, hepatitis, liver cirrhosis, tumors, pneumonia, and sepsis [9][10][11][12][13].…”