Abstract
BackgroundImmunotherapy with PD-1 antibodies has greatly increased prognosis of patients with advanced melanoma. Identifying biomarkers that predict overall survival (OS) and response to immunotherapy is important.MethodsOS and best overall response according to RECIST version 1.1 were analysed, and S100B and lactate dehydrogenase (LDH) serum levels were assessed retrospectively in 152 patients treated with anti-PD-1, and in 86 patients treated with anti-PD-1 plus anti-CTLA-4 antibodies at University Hospital Tuebingen, Germany.ResultsIn the pembrolizumab group, patients with elevated baseline S100B or LDH exhibited significantly impaired OS compared with patients with normal S100B (1-year OS: 51.1% vs 83.1%, log-rank P < .0001) and normal LDH (1-year OS: 44.4% vs 80.8%, P = .00022), respectively. LDH increases of >25% and S100B increases of >145% compared to baseline were significantly associated with impaired OS (both P < .0001). In patients treated with ipilimumab and nivolumab, baseline S100B and increasing S100B levels of >145% as well as baseline LDH were associated with impaired OS (P < .0001, P = .00060, and P = .0050, respectively), whereas increasing LDH of >25% was not (P = .64).ConclusionsS100B could serve as a strong baseline marker for OS in melanoma patients receiving anti-PD-1 therapy. Rising S100B levels during the first weeks of therapy could help guide treatment decisions.
Highlights
Anti-programmed death receptor-1 antibodies alone or in combination with cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibodies have improved the prognosis of metastatic melanoma substantially and have been shown to induce long-lasting partial or complete responses in melanoma patients.[1,2,3] primary or acquired resistance against immune checkpoint inhibitors occurs in 50–60% of the patients.[4]
In patients treated with the combined immunotherapy with ipilimumab and nivolumab, lactate dehydrogenase (LDH) increases were not associated with impaired overall survival (OS) (HR 1.21, 95% CI 0.55–2.67, P = .64), whereas S100B increases were again significantly associated with impaired OS (HR 3.65, 95% CI 1.66–8.03, P = .00060) (Fig. 3b, d, and Supplementary Figures S4 and S5)
Our study shows that patients with elevated levels of LDH > 1.5 × upper limit of normal (ULN) and S100B > 0.3 μg/l exhibit significantly diminished OS compared with those patients with lower levels of LDH and
Summary
Anti-programmed death receptor-1 (anti-PD-1) antibodies alone or in combination with cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibodies have improved the prognosis of metastatic melanoma substantially and have been shown to induce long-lasting partial or complete responses in melanoma patients.[1,2,3] primary or acquired resistance against immune checkpoint inhibitors occurs in 50–60% of the patients.[4]. Serum lactate dehydrogenase (LDH) is a well-known biomarker for metastatic melanoma patients and since 2009 a part of the revised melanoma staging guidelines from the American joint committee on cancer (AJCC).[5,6,7,8] In recent trials with immune checkpoint inhibitors elevated baseline LDH had consistently been shown to correlate with poor survival and poor response rates.[3,9] a retrospective study on 66 patients receiving the PD-1 antibodies nivolumab or pembrolizumab reported that increases in LDH levels between start of treatment and the first staging were associated with poor response and diminished overall survival (OS).[10]. Rising S100B levels during the first weeks of therapy could help guide treatment decisions
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