Abstract
The treatment and prognosis of metastatic melanoma have changed during the last decade to include immunotherapy or targeted therapy as standard therapeutic options for BRAF-mutated melanoma. However, predictive and/or prognostic markers are lacking, especially in clinical situations where several options are available. The aim of this study was to determine the association of pre-therapeutic blood cell count-derived ratios (BCDR) with survival in patients with BRAF-mutated metastatic melanoma. We evaluated the prognostic role of BCDR in therapy-naïve patients with BRAF-mutated metastatic melanoma treated with immune checkpoint inhibitors or targeted therapy. The impact of BCDR on survival was analysed using univariate and multivariate Cox proportional hazard models. We enrolled 46 patients treated with BRAF inhibitors and 20 patients who received anti-PD-1 checkpoint inhibitors. The median progression-free survival (PFS) and overall survival (OS) were 8.3 and 18.2 months, respectively, with no statistical difference between groups. The objective response rate was 39% (30% in the anti-PD-1 and 44% in the targeted therapy groups). Baseline BCDR values were associated with improved PFS and OS in the immunotherapy group. Only the platelet-to-lymphocyte ratio (PLR) was associated with OS and PFS in the targeted therapy group. Independent prognostic indicators for PFS were lactate dehydrogenase, PLR and the lymphocyte-to-monocyte ratio (LMR) and those for OS were LMR, toxicity and the number of initial metastases. BCDR had a substantial prognostic value in patients with BRAF-mutated metastatic melanoma treated with immune checkpoint inhibitors. However, a prognostic role for BCDR seemed less apparent in patients treated with targeted therapies.
Highlights
Treatment of advanced/metastatic melanoma has dramatically changed during the last decade with the introduction of the immune-checkpoint inhibitors anti-Cytotoxic T-lymphocyte antigen 4 (CTLA-4) in 2010 and later anti-progressive disease (PD)-1
Our results support a prognostic value of blood cell count–derived ratios (NLR, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and systemic inflammation index (SII)) in B-Raf proto-oncogene (BRAF) mutant metastatic melanoma patients treated with immune checkpoint inhibitors
The evaluation of baseline blood cell count–derived ratios should be considered in all patients treated with immunotherapy
Summary
Treatment of advanced/metastatic melanoma has dramatically changed during the last decade with the introduction of the immune-checkpoint inhibitors anti-CTLA-4 in 2010 (ref.1) and later anti-PD-1 (ref.[2,3]). The subsequent introduction of selective inhibitors of the B-Raf proto-oncogene BRAF (BRAFi), such as vemurafenib, dabrafenib, and encorafenib[4,5,6], and their combination with mitogenactivated protein kinases (MEK) inhibitors, such as cobimetinib, trametinib, and binimetinib[6,7,8], have opened up further targeted treatment possibilities for a group of melanoma patients with BRAF mutations These new therapeutics have significantly improved the prognosis of metastatic melanoma, but both immunotherapy and targeted approaches have their advantages and disadvantages. We evaluated the prognostic role of BCDR in therapy-naïve patients with BRAF-mutated metastatic melanoma treated with immune checkpoint inhibitors or targeted therapy. A prognostic role for BCDR seemed less apparent in patients treated with targeted therapies
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