Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab

Ferrucci, Pier Francesco; Ascierto, Paolo A.; Pigozzo, Jacopo; Vecchio, Michele Del; Maio, Michele; Cappellini, Gian Carlo Antonini; Giusti, Massimo; Queirolo, Paola; Savoia, Paola; Mandalà, Mario; Simeone, Ester; Valpione, Sara; Altomonte, Maresa; Spagnolo, Francesco; Cocorocchio, Emilia; Gandini, Sara; Giannarelli, Diana; Martinoli, Chiara

doi:10.1093/annonc/mdw016

Cited by 328 publications

(236 citation statements)

References 22 publications

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“…Recently, Ferrucci et al found the baseline NLR to be strongly and independently associated with progression free and overall survival following the treatment with anti-CTLA4 antibody. Specifically, they found that an NLR ≥ 3 had a significantly and independently increased risk of death [hazard ratio (HR) = 5.76; 95% CI 4.29-7.75] and of progression (HR = 4.10; 95% CI 3.08-5.46) compared with patients with a lower NLR [6, 25]. However, whether NLR remains a general prognostic factor or predictive for ipilimumab benefit in the metastatic setting remains unclear.…”

Section: Discussionmentioning

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

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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.

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Section: Discussionmentioning

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

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“…Until now predictive biomarkers of sorafenib efficacy or resistance have yet to be identified [8, 9, 10, 11, 12, 13]. …”

Section: Introductionmentioning

confidence: 99%

Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib

et al. 2016

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We evalueted a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the aim to explored their prognostic value in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. 56 advanced HCC patients receiving sorafenib were available for our analysis. Lymphocyte, neutrophil and platelet were measured before beginning of treatment and after one month. Patient with SII ≥ 360 showed lower median PFS (2.6 vs. 3.9 months, P < 0.026) and OS (5.6 vs. 13.9 months, P = 0.027) with respect to patients with SII < 360.NLR ≥ 3 had a lower median PFS (2.6 vs. 3.3 months, P < 0.049) but not OS (5.6 vs. 13.9 months, P = 0.062) than those with NLR < 3. After adjusting for clinical covariates SII and NLR remained an independent prognostic factor for OS. The SII and NLR represent potential prognostic indicator in patients with advanced HCC treated with sorafenib.

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“…Biomarker, die die Wirksamkeit von Ipilimumab vorhersagen, werden für Patienten mit CRPC dringend benötigt, aber leider wurde bislang nur wenig Forschung zu diesem Thema vorgelegt. Beim Melanom sind hohe Ausgangsspiegel der Laktat-Dehydrogenase [15,16], eine hohe Anzahl von Neutrophilen und hohes Verhältnis von Neutrophilen zu Lymphozyten [17,18] bei Patienten unter Ipilimumab mit schlechteren Ergebnissen assoziiert, obwohl sie nicht unbedingt prädiktiv für die Wirksamkeit der Behandlung sind. Bei Männern mit CRPC, die Ipilimumab erhalten, ist die Anzahl der CD4-T-Lymphozyten, die PD-1 exprimieren, mit dem Behandlungsergebnis assoziiert [18,19], obwohl nicht bekannt ist, ob dieser Parameter für einen Behandlungsvorteil prädiktiv ist.…”

Section: Diskussionunclassified

Langfristige Vollremission mit Ipilimumab bei metastasiertem kastrationsresistentem Prostatakrebs: Fallbericht von zwei Patienten

Cabel¹,

Loir²,

Gravis³

et al. 2018

Kompass Onkol

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Hintergrund: Prostatakrebs ist eine der häufigsten Krebserkrankungen bei Männern und die vierthäufigste Ursache für Krebssterblichkeit weltweit. Obwohl in den letzten Jahren mit auf die Androgenrezeptorachse gezielten Wirkstoffen der nächsten Generation, Taxanen und auf die Knochen gerichteten Mitteln große Fortschritte bei Patienten mit metastasiertem kastrationsresistentem Prostatakrebs (mCRPC, metastatic castrate-resistant prostate cancer) erzielt wurden, ist die Immuntherapie noch nicht allgemein zur Behandlung von Prostatakrebs zugelassen und in Gebrauch. Zwei große Studien mit Ipilimumab, einem Antikörper gegen CTLA-4 (zytotoxisches T-Lymphozyten-Antigen 4), zeigten verbessertes progressionsfreies Überleben, aber kein statistisch verbessertes Gesamtüberleben bei der Primäranalyse (CA184 043 und CA184 095). Fallvorstellung: Hier berichten wir über zwei Patienten, die in diesen Studien Ipilimumab erhielten und immer noch in langfristiger Vollremission bei einer Nachbeobachtungszeit von 64 bzw. 52 Monaten nach Beginn der Behandlung mit Ipilimumab sind. Immunhistochemische Färbung auf hMLH1, hMSH2, hMSH6 und PMS2 wurde an archivierten Prostatabiopsieproben von einem der beiden Patienten durchgeführt; sie zeigten eine normale Proteinexpression. Interessanterweise wurde bei diesem Patienten in archivierten Prostatabiopsien hohe Infiltration mit CD3+- und CD8+-T-Zellen beobachtet, ebenso wie mit regulatorischen FoxP3⁺-T_reg-Zellen. Schlussfolgerung: Ipilimumab zeigt klinische Aktivität bei Patienten mit CRPC, einschließlich Fällen sehr langen Ansprechens ohne nachweisbare Resterkrankung. Übersetzung aus J Immunother Cancer 2017;5:31.

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Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab

Cited by 328 publications

References 22 publications

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

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

Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib

Langfristige Vollremission mit Ipilimumab bei metastasiertem kastrationsresistentem Prostatakrebs: Fallbericht von zwei Patienten

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