Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients

Ferrucci, Pier Francesco; Gandini, Sara; Battaglia, Agatino; Alfieri, Salvatore; Giacomo, Anna Maria Di; Giannarelli, Diana; Cappellini, Gian Carlo Antonini; Galitiis, Federica De; Marchetti, Paolo; Amato, Giovanni; Lazzeri, Andrea; Pala, Laura; Cocorocchio, Emilia; Martinoli, Chiara

doi:10.1038/bjc.2015.180

Cited by 200 publications

(178 citation statements)

References 25 publications

Supporting

Mentioning

165

Contrasting

Unclassified

Order By: Relevance

“…Also, the separate analysis of patients without CNS metastases did not change these results. Baseline NLR represents an independent prognostic factor for cancer immunotherapy outcomes, and high values (cutoff 4 or 5) correlate with worse treatment responses (32,45). In our study, we did not find significant differences of baseline NLR values between the two treatment groups.…”

Section: Discussioncontrasting

confidence: 53%

Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma

Theurich

Rothschild

Hoffmann

et al. 2016

Cancer Immunology Research

129

View full text Add to dashboard Cite

Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n ¼ 82) or ipilimumab and additional LPT (n ¼ 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P ¼ 0.0028). Adverse immunerelated events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31-1.01, P ¼ 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation.

show abstract

Section: Discussioncontrasting

confidence: 53%

Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma

Theurich

Rothschild

Hoffmann

et al. 2016

Cancer Immunology Research

129

View full text Add to dashboard Cite

show abstract

“…Recently, the direct relationship between cancer related inflammation and oncologic outcome has become evident [6, 7]. Systemic inflammation is tied to alterations in circulating peripheral blood leukocytes.…”

Section: Introductionmentioning

confidence: 99%

“…An easily obtainable, pre-treatment biomarker of systemic inflammation is the peripheral blood neutrophil-to-lymphocyte ratio (NLR). An elevated NLR has been associated with poor prognosis in a number of solid organ malignancies including colorectal, esophageal, gastric, pancreatic, and primary liver cancers, gastrointestinal stromal tumor and other soft tissue sarcomas, and metastatic melanoma [6, 8–15]. The aims of this study are to characterize the outcomes of patients with high-risk, non-metastatic melanoma, to determine if NLR correlates with known prognostic factors, and to examine the association of preoperative NLR with long-term outcome.…”

Section: Introductionmentioning

confidence: 99%

Elevated Blood Neutrophil-to-Lymphocyte Ratio: A Readily Available Biomarker Associated with Death due to Disease in High Risk Nonmetastatic Melanoma

et al. 2017

View full text Add to dashboard Cite

Background Elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is associated with poor oncologic outcomes in patients with stage IV melanoma and other solid tumors, but its impact has not been characterized for patients with high-risk, non-metastatic melanoma. Methods Retrospective review of a melanoma database identified patients with high-risk melanoma who underwent operation with curative intent at a single institution. NLR was calculated from blood samples obtained within two-weeks prior to operation. Multiple primary melanomas and concurrent hematologic or other metastatic malignancies were excluded. Cumulative incidence of death due to disease was estimated, and Gray’s test was used to examine the effect of NLR on melanoma disease specific death (DOD). Multivariable competing risks regression models assessed associated factors. Results Data on 1,431 patients with high-risk non-metastatic melanoma were analyzed. Median follow-up for survivors was 4 years. High NLR (≥3 or as continuous variable) was associated with older age, male sex, thicker primaries, higher mitotic index and more advanced nodal status. On multivariate analysis, high NLR (≥ 3 or as a continuous variable), older age, male sex, ulcerated primary, lymphovascular invasion and positive nodal status were all independently associated with worse DOD. Conclusions NLR is a readily available blood test that was independently associated with DOD in patients with high risk non-metastatic melanoma. It is unclear whether high NLR is a passive indicator of poor prognosis, or a potential therapeutic target. Further studies to evaluate the prognostic role of NLR to potentially identify those more likely to benefit from adjuvant immunotherapy may prove informative.

show abstract

“…These hypotheses have been validated in multiple studies on ipilimumab-treated melanoma, in which elevated NLR was associated with decreased survival [6] [15] [16]. Additionally, a retrospective review of ipilimumab-treated melanoma patients similarly determined dNLR of 3 to be the ideal cutoff point and associated elevated dNLR with shortened survival [9].…”

Section: Discussionmentioning

confidence: 91%

“…The pretreatment neutrophil-to-lymphocyte ratio (NLR) has been correlated with overall survival (OS) and progression free survival (PFS) in a wide range of malignancies, including melanoma patients treated with the immune-checkpoint inhibitor ipilimumab [6] [7] [8]. The derived NLR (dNLR), a formula involving exclusively white blood cell (WBC) count and Absolute Neutrophil Count (ANC), is an alternative to NLR when only WBC and ANC are available.…”

Section: Introductionmentioning

confidence: 99%

Prognostic and Predictive Value of Pretreatment Derived Neutrophil-to-Lymphocyte Ratio in Non-Small-Cell Lung Cancer Patients Treated with an Immune Checkpoint Inhibitor

Kucharczyk¹,

Sullivan²,

Lu³

et al. 2018

JCT

View full text Add to dashboard Cite

Background: Immune checkpoint inhibitors produce prolonged responses in select non-small cell lung cancer (NSCLC) patients, however the identification of patients most likely to benefit is difficult. Pretreatment derived neutrophil-to-lymphocyte ratio (dNLR) is an easily calculated marker available in routine clinical care that has shown prognostic value in many cancer treatment settings, but its association with survival in NSCLC patients treated with immune-checkpoint inhibitors is less understood. Patients and Methods: We retrospectively reviewed 72 NSCLC patients receiving either nivolumab or pembrolizumab between 3/1/15 and 3/1/17 with a median follow-up time of 5.1 months. Patients were compared using Cox proportional hazards models to detect an association between pretreatment dNLR < 3 vs ≥3 on overall survival (OS), progression-free survival (PFS) and overall response rate. Results: Median age was 65 (range: 41 -86), 65% were male, 40% received ≥

show abstract

Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients

Cited by 200 publications

References 25 publications

Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma

Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma

Elevated Blood Neutrophil-to-Lymphocyte Ratio: A Readily Available Biomarker Associated with Death due to Disease in High Risk Nonmetastatic Melanoma

Prognostic and Predictive Value of Pretreatment Derived Neutrophil-to-Lymphocyte Ratio in Non-Small-Cell Lung Cancer Patients Treated with an Immune Checkpoint Inhibitor

Contact Info

Product

Resources

About