Serum lactate dehydrogenase (LDH) as a prognostic selection criterion for ipilimumab treatment in metastatic melanoma.

Abstract

3036 Background: Ipilimumab, a CTLA4 blocking antibody, has been shown to improve survival in metastatic melanoma patients in phase III trials. However, only a subset of patients experiences long-term survival benefit. Therefore, we analysed two independent retrospective sets of patients treated in ‘real world’ settings to identify prognostic factors that correlate with better outcome after ipilimumab therapy. Methods: Advanced melanoma patients, eligible for ipilimumab therapy, were treated in the Dutch and UK Expanded Access Programs (EAP) and after European licensing on the 3mg/kg schedule. Baseline characteristics and peripheral blood parameters were assessed and patients were monitored for the occurrence of adverse events and responses. Results: A total of 166 patients were enrolled in the Dutch EAP. Best overall response rate and disease control rate were (DCR) 17% and 35%. Median follow-up was 17.9 months, with a median progression free survival of 2.9 months. Median overall survival (OS) was 7.5 months, and OS at 1 year 37.8% and at 2 years 22.9%. Univariate analysis revealed that gender, age, Breslow thickness, baseline and week 6 lymphocyte count (ALC), and prior treatment had no influence on OS, while mWHO, M stage, baseline LDH, S100, erythrocyte sedimentation rate (ESR), and the slope of ALC did. In a multivariate model only baseline LDH and ESR remained as significant independent prognostic factors. The relevance of LDH was validated in an independent cohort of 68 patients from the UK. Stratifying the patients in the NL cohort according to LDH levels (≤upper limit normal (ULN), 54.4% of patients versus >2xULN, 16.9% of patients) separated into groups of patients observing DCR of 48% versus 14%, and median OS of 13.7 versus 3.1 months, while toxicity was similar in both groups (48% and 41%). None of the patients was alive at 15 months after treatment if baseline LDH was >2xULN in both the NL and UK cohorts. Conclusions: Overall survival upon ipilimumab treatment is lower in an expanded access population as compared to phase III trials. LDH >2xULN at baseline is a potential prognosticator in patients receiving ipilimumab and should be considered in guiding ipilimumab treatment initiation.