Lactate dehydrogenase and baseline markers associated with clinical outcomes of advanced esophageal squamous cell carcinoma patients treated with camrelizumab (SHR‐1210), a novel anti‐PD‐1 antibody

Abstract

Background A small proportion of patients with advanced esophageal squamous cell carcinoma (ESCC) could benefit from immune checkpoint inhibitors; however, reliable peripheral blood biomarkers for outcomes of anti‐PD‐1 immunotherapy in ESCC have not been identified. Methods The data of 43 patients in the ESCC cohort of a phase I trial at our center were retrospectively reviewed. All patients were administered intravenous camrelizumab (SHR‐1210), a novel anti‐PD‐1 antibody, at doses of 60 mg, 200 mg, or 400 mg (4‐week interval after first dose followed by a 2‐week schedule) until disease progression or intolerable toxicity. Associations between lactate dehydrogenase (LDH) and other peripheral blood biomarkers at baseline and the efficacy of camrelizumab were also investigated. Results After median follow‐up of 19.6 months, the overall response rate was 25.6% (11/43), including one complete response. Median progression‐free and overall survival rates were 2.0 and 8.0 months, respectively. Patients with an elevated baseline LDH had lower tumor response rates ( P = 0.02) and shorter progression‐free ( P = 0.002) and overall ( P < 0.0001) survival than patients with normal LDH levels. An increase in LDH levels during treatment was significantly associated with disease progression. Multivariate Cox analysis identified LDH (hazard ratio [HR] 0.18), CRP (HR 0.27), the number of organs involved (HR 0.31), absolute monocyte count (HR 0.33), and Eastern Cooperative Oncology Group performance status (HR 0.36) as independent prognostic factors. Conclusions Serum LDH, which is readily available in routine clinical practice, is a potential marker for response and a powerful independent factor for survival in advanced ESCC patients treated with anti‐PD‐1 therapy.

Prognostic Significance of Baseline Neutrophil Count and Lactate Dehydrogenase Level in Patients With Esophageal Squamous Cell Cancer Treated With Radiotherapy

“…Neutrophil count and LDH both routinely detected the hematological index and were easily available in our clinical practice. Previous studies have investigated the prognostic value of LDH level, neutrophil count, and NLR in many solid tumors (10,21,24). However, there was no investigation about the role of the LDH level combined with neutrophil count or NLR in the prognosis of ESCC patients treated with radiotherapy.…”

“…A meta-analysis investigating the prognostic value of the LDH level in solid tumors showed that a high LDH level is associated with poor survival in melanoma, gastric, lung cancer, prostate, and renal cell carcinomas (34). Recently, a high LDH level has been demonstrated to effectively predict the response to cancer treatment, such as chemotherapy (11), anti-angiogenetic agents (35), and checkpoint immunotherapy (22,24) in various cancers. The prognostic role of the LDH level was also investigated in ESCC patients who underwent curative treatment in the study from Wei et al (23).…”

“…However, the predictive value of neutrophil count in the prognosis of ESCC patients treated with radiotherapy is still unclear. Recently, the prognostic value of LDH has been widely investigated in various cancers, such as metastatic renal cell carcinoma (17), breast cancer (18), nasopharyngeal carcinoma (19), prostate cancer (20), lymphoma (21), non-small cell lung cancer (22), and ESCC (23,24). Although LDH and neutrophil count are reliable prognostic predictors, it is still not clear whether they can be combined together in a prognostic risk score model to predict the prognosis of ESCC patients treated with radiotherapy.…”

A New Risk Score Model Based on Lactate Dehydrogenase Predicting Prognosis in Esophageal Squamous Cell Carcinoma Treated With Chemoradiotherapy

“…[8][9][10][11][12][13][14]25 Several studies also have evaluated the prognostic value of LDH in ESCC. [15][16][17][18][19][20] Nevertheless, the prognostic role for pretreatment serum LDH in ESCC remains uncertain until now. The current study demonstrated that lower LDH levels were associated with a better prognosis compared with higher LDH levels, as shown in both multivariable analysis based on the whole cohort of 614 patients and the propensity score-matched cohort of 256 patients.…”

“…14 Several investigators also scrutinized the prognostic value of LDH in ESCC. [15][16][17][18][19][20] However, owing to the inconsistent conclusions, serum LDH is a controversial prognostic biomarker for prognosis in ESCC and needs to be further investigated. Furthermore, studies on the in uence of LDH on the prognosis are still lacking for patients with ESCC underwent chemoradiotherapy.…”