Background: An anti-programmed cell death protein 1 monoclonal antibody, nivolumab, is one of the most effective drugs for advanced melanoma. Tumor cellderived or immune cell-derived markers and clinical predictors such as serum lactate dehydrogenase (LDH) and cutaneous adverse events, have already been described as prognostic factors for advanced melanoma treated with nivolumab. We sought to identify further clinical predictors that can be determined in routine clinical practice. Methods: We retrospectively analyzed clinical findings of 98 consecutive patients with unresectable stage III or IV melanoma treated with nivolumab, at the National Cancer Center Hospital or at Keio University Hospital, in Tokyo, Japan, between July 2014 and July 2016. These patients had been administered nivolumab at a dose of 2mg/kg every 3 weeks. Results: As for pretreatment prognostic factors, ECOG performance status (PS) ≥1, maximum tumor diameters of = 30mm, elevated LDH and elevated C-reactive protein were significantly associated with poor overall survival (OS) (hazard ratio [HR] 0.29 [P < 0.001], HR 0.40 [p = 0.003], HR 0.29 [P < 0.001], HR 0.42 [P = 0.004], respectively) on univariate analysis. Among these factors, PS and LDH were identified as independent variables by multivariate analysis. As for early markers examined during therapy, patients with absolute lymphocyte count (ALC) = 1000/μl (Week3: HR 0.40 [P = 0.004], Week6: HR 0.33 [P = 0.001]) and absolute neutrophil count (ANC) < 4000/μl (Week3: HR 0.46 [P = 0.014], Week6: HR 0.51 [P = 0.046]) had significantly better OS. Conclusion: ALC≥1000/μl and ANC < 4000/μl during treatment appear to be early markers associated with OS. Nivolumab might have minimal efficacy in patients with a massive tumor burden.
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