A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab

Abstract

Background: Pembrolizumab improves the survival of patients with advanced melanoma. A comprehensive analysis of baseline variables that predict the benefit of pembrolizumab monotherapy has not been conducted. Methods: Survival data of patients with advanced melanoma who were treated with pembrolizumab in a single university hospital were collected. A multivariate Cox regression analysis was performed to correlate baseline clinical, laboratory, and radiologic characteristics and NanoString IO360 gene expression profiling (GEP) with survival. Results: 183 patients were included (stage IV 85.2%, WHO performance status ≥1 31.1%; pembrolizumab first-line 25.7%), of whom 112 underwent baseline 18F-FDG-PET/CT imaging, 58 had circulating tumor DNA (ctDNA) assessments, and GEP was available in 27 patients. Active brain metastases, a higher number of metastatic sites, lower albumin and absolute lymphocyte count (ALC), higher C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio, higher total metabolic tumor volume (TMTV), and higher ctDNA levels were associated with worse survival. Elevated lactate dehydrogenase (LDH) ≥ 2ULN (upper limit of normal), CRP ≥ 10ULN, or ALC < 750/mm3 delineate a subpopulation where treatment with pembrolizumab is futile. A TMTV ≥ 80 mL encompassed 17/21 patients with LDH ≥ 2ULN, CRP ≥ 10ULN, or ALC < 750/mm3. No significant associations were observed between baseline GEP scores and survival. Conclusion: Multiple baseline variables correlate with survival on pembrolizumab. TMTV is a more comprehensive baseline biomarker than CRP, LDH, or ALC in predicting the futility of pembrolizumab.

Prognostic value of 2-[18F]FDG PET-CT in metastatic melanoma patients receiving immunotherapy

“…Prior studies of melanoma patients, received targeted therapies, identified the number of metastatic organ sites or the number of lesions along with baseline LDH level as predictive factors for PFS and OS [42,43]. Our findings also indicated that the total number of metastatic lesions and their numbers in the abdomen and pelvis in the 3-month follow-up scan were among the fourteen most predictive values for the 5-year survival rate.…”

Circulating extracellular vesicles expressing PD1 and PD-L1 predict response and mediate resistance to checkpoint inhibitors immunotherapy in metastatic melanoma

“…Considering the influence of gender [ 43 ] and the number of metastasis [ 44 ], our analysis showed no differences in the percentage of PD1 + EVs with the only exception of those released by DCs which showed a slight increase in responders vs non-responders. Conversely, if we consider the possible correlation between PD1 + EVs and these two parameters as a function of the response to immunotherapy, we always found a notable increase in PD1 + EVs in the plasma of the non-responders of both subgroups (Supplemental Fig.…”

Early Reassessment of Total Metabolic Tumor Volume on FDG-PET/CT in Advanced Melanoma Patients Treated with Pembrolizumab Predicts Long-Term Outcome

“…Also, high LDH levels, the number of metastatic sites, and previous treatment with systemic therapies have a negative effect. Other biochemical and immunohistochemical analyses are being studied to determine their capability to predict response to ICI and therefore outcome [9]. Our aim was to demonstrate whether changes in metabolic tumor volume assessed by FDG-PET/CT could be used to predict the long-term efficacy of Pembrolizumab.…”

“…A relationship has already been demonstrated between outcome and various clinical factors such as certain previous treatments (for example Ipilimumab and BRAF-/MEK-inhibitors), presence of brain metastases, and the number of metastatic locations. Immunohistochemical analysis also shows promising results for the prediction of outcomes [9].…”