Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma

Abstract

Background:Treatment with programmed death receptor-1 (PD-1) antibodies is associated with high response rates in patients with advanced melanoma. Reliable markers for early response and outcome are still sparse.Methods:We evaluated 66 consecutive patients with advanced/metastatic melanoma treated with nivolumab or pembrolizumab between 2013 and 2014. The main objectives of this study were to investigate whether, first, serum lactate dehydrogenase (LDH) at baseline (normal vs above the upper limit of normal) correlates with overall survival (OS), and, second, whether the change of LDH during treatment predicts response before the first scan and OS in patients with an elevated baseline LDH.Results:After a median follow-up of 9 months, patients with an elevated baseline LDH (N=34) had a significantly shorter OS compared with patients with normal LDH (N=32; 6-month OS: 60.8% vs 81.6% and 12-month OS: 44.2% vs 71.5% (log-rank P=0.0292). In those 34 patients with elevated baseline LDH, the relative change during treatment was significantly associated with an objective response on the first scan: the 11 (32%) patients with partial remission had a mean reduction of −27.3% from elevated baseline LDH. In contrast, patients with progressive disease (N=15) had a mean increase of +39%. Patients with a relative increase over 10% from elevated baseline LDH had a significantly shorter OS compared with patients with ⩽10% change (4.3 vs 15.7 months, log-rank P<0.00623).Conclusions:LDH could be a useful marker at baseline and during treatment to predict early response or progression in patients with advanced melanoma who receive anti-PD-1 therapy.

Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy

“…As previously described, several potential biomarkers for nivolumab have been suggested in recent years [5–18]. As to routinely-obtained clinical findings, only cutaneous AEs and LDH have been reported [17, 18].…”

“…However, these biomarkers are not entirely reliable and their investigation is labor-intensive and thus impractical in daily clinical practice. On the other hand, predictors which are also routinely obtained clinical findings, such as serum lactate dehydrogenase (LDH) and cutaneous adverse events (AEs), have only been assessed by a small number of investigators [17, 18]. …”

Monitoring immune-checkpoint blockade: response evaluation and biomarker development

“…In 80% (12/15) of patients with no response, the baseline levels of CD45RO + /CD8 + T cells were ≤25%, whereas all (6/6) patients with a response had ≥30% CD45RO + /CD8 + T cells 81 . In addition, elevated pretreatment levels of LDH were shown to be negatively associated with overall survival in patients with melanoma treated with ipilimumab or pembrolizumab 76–78,82,83 .…”

Biomarkers in Malignant Melanoma: Recent Trends and Critical Perspective

“…An independent study showed that low baseline serum LDH is associated with favorable outcome of latestage 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.…”