Neutrophil to Lymphocyte Ratio is Associated With Outcome During Ipilimumab Treatment.

Ipilimumab (IPI) and BRAF inhibitors (BRAFi) improve survival in melanoma, but not all patients will benefit and toxicity can be significant. Pretreatment neutrophil to lymphocyte ratio (NLR) has been associated with outcome in IPI-treated patients, but has not been studied during treatment or in BRAFi-treated patients. Using a prospectively maintained database, patients with unresectable stage III or IV melanoma treated with IPI or a BRAFi (vemurafenib or dabrafenib as monotherapy) from 2006 to 2011 were identified. NLR was calculated before treatment and at 3-week intervals after treatment initiation until 9weeks. Baseline NLR was tested for association with overall survival (OS), progression free survival (PFS), and clinical response to treatment. On-treatment NLRs were tested for association with the same outcomes using landmark survival analyses and time-dependent Cox regression models. The association of relative change of NLR from baseline with outcomes was also examined. A multivariate model tested the association of NLR and OS/PFS with additional clinical factors. There were 197 IPI patients and 65 BRAFi patients. In multivariable analysis adjusting for M stage, and disease type (in OS)/gender (in PFS), an NLR value of 5 or above at every timepoint was associated with worse OS (HR 2.03-3.37, p<0.001), PFS (HR 1.81-2.51, p<0.001), and response to therapy (OR 3.92-9.18, p<0.007), in the IPI cohort. In addition, a >30% increase in NLR above baseline at any timepoint was associated with a worse OS and PFS (HR 1.81 and 1.66, p<0.004). In BRAFi patients, NLR was not consistently associated with outcomes. A high NLR, whether measured prior to or during treatment with IPI, is associated with worse OS, PFS, and clinical response in patients with advanced melanoma. An increasing NLR from baseline during treatment was correlated with worse OS and PFS in IPI-treated patients. In comparison, as NLR was not associated with outcomes in BRAFi patients, NLR may have a uniquely predictive value in patients treated with immunotherapy.

Cassidy MR ，Wolchok RE ，Zheng J ，Panageas KS ，Wolchok JD ，Coit D ，Postow MA ，Ariyan C ... -  《EBioMedicine》

A high neutrophil to lymphocyte ratio prior to BRAF inhibitor treatment is a predictor of poor progression-free survival in patients with metastatic melanoma.

Finon A ，Zaragoza J ，Maillard H ，Beneton N ，Bens G ，Samimi M ，Caille A ，Machet L ... -  《-》

Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors.

The immunotherapy (IT) agents ipilimumab and interleukin-2 as well as BRAF inhibitors (BRAFi) vemurafenib and dabrafenib, with or without trametinib (MEK inhibitors), are all FDA-approved treatments for BRAF metastatic melanoma, but there are few studies to guide optimal sequencing. This retrospective analysis describes the outcomes of patients treated with either BRAFi before IT or IT before BRAFi. A cohort of patients treated with BRAFi alone or with MEK inhibitor was retrospectively identified. Response rate (RR), overall survival (OS), and progression-free survival (PFS) were evaluated for the entire cohort, subdivided by BRAFi prior to or after IT. RR and median PFS and OS calculated from commencement of BRAFi following IT (N = 32) were 57%, 6.7 months (95% confidence interval [CI] = 4.3-9.1 months), and 19.6 months (95% CI = 10.0-undefined months), respectively; whereas for BRAFi initially (N = 242) were 66%, 5.6 months (95% CI = 4.7-6.8 months), and 13.4 months (95% CI = 10.1-17.0 months). Results were similar when controlled for prognostic variables. A total of 193 patients discontinued BRAFi, with OS of 2.9 months (range of 1.8-4.4 months) from day of BRAFi discontinuation. Forty patients subsequently received IT with ipilimumab. Only half could complete 4 doses of ipilimumab; PFS with ipilimumab was 2.7 months (95% CI = 1.8-3.1 months) and OS was 5.0 months (95% CI = 3.0-8.8 months). In this retrospective analysis, prior treatment with IT does not appear to negatively influence response to BRAFi. Outcomes for IT with ipilimumab following BRAFi discontinuation are poor. Randomized controlled trials are needed to define if sequencing IT prior to BRAFi therapy is superior to sequencing BRAFi prior to IT.

Ackerman A ，Klein O ，McDermott DF ，Wang W ，Ibrahim N ，Lawrence DP ，Gunturi A ，Flaherty KT ，Hodi FS ，Kefford R ，Menzies AM ，Atkins MB ，Long GV ，Sullivan RJ ... -  《-》

Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab.

Capone M ，Giannarelli D ，Mallardo D ，Madonna G ，Festino L ，Grimaldi AM ，Vanella V ，Simeone E ，Paone M ，Palmieri G ，Cavalcanti E ，Caracò C ，Ascierto PA ... -  《Journal for ImmunoTherapy of Cancer》

High baseline neutrophil-to-lymphocyte ratio predicts worse outcome in patients with metastatic BRAF-positive melanoma treated with BRAF and MEK inhibitors.

Teterycz P ，Jagodzińska-Mucha P ，Cybulska-Stopa B ，Mariuk-Jarema A ，Kozak K ，Koseła-Paterczyk H ，Czarnecka AM ，Rajczykowski M ，Dziura R ，Galus Ł ，Mackiewicz J ，Świtaj T ，Klimczak A ，Falkowski S ，Suwiński R ，Ziobro M ，Ługowska I ，Rutkowski P ... -  《-》