Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab

Fujisawa, Yasuhiro; Yoshino, Koji; Otsuka, Atsushi; Funakoshi, Takeru; Fujimura, Taku; Yamamoto, Yuki; Hata, Hiroo; Gosho, Masahiko; Tanaka, Ryota; Yamaguchi, Kensei; Nonomura, Yumi; Hirai, Ikuko; Furudate, Sadanori; Okuhira, Hisako; Imafuku, Kimiaki; Aoki, Megumi; Matsushita, Satoru

doi:10.1016/j.jdermsci.2017.07.007

Cited by 82 publications

(83 citation statements)

References 32 publications

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“…These findings suggest the importance of predicting irAEs to avoid severe complications using simple methods. Indeed, Fujisawa et al [ 26 ] reported that the decrease of lymphocytes fraction could predict irAEs caused by nivolumab, but only in the very short period before irAE development. Since the interval for nivolumab administration is 2 or 3 weeks for melanoma patients, other prognostic biomarkers are needed for long intervals.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study

et al. 2018

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Antibodies against PD-1, such as nivolumab and pembrolizumab, are widely used in the treatment of various cancers including advanced melanoma. The anti-PD-1 Ab significantly prolongs survival in patients with metastatic melanoma, and its administration in combination with local or systemic therapy may also lead to improved outcomes. Although anti-PD-1 Ab-based combined therapy might be effective for the treatment of advanced melanoma, the associated risk of irAEs is an important consideration. Therefore, being able to predict irAEs is of great interest to oncologists. The purpose of this study was to evaluate the value of using serum levels of sCD163 and CXCL5 to predict irAEs in patients with advanced melanoma who were administered nivolumab. To this end, we analyzed these serum levels in 46 cases of advanced melanoma treated with nivolumab. In addition, the tumor stroma was evaluated by immunohistochemistry and immunofluorescence. We measured the serum levels of sCD163 and CXCL5 on day 0 (immediately before nivolumab administration) and day 42. The serum absolute levels of sCD163 were significantly increased in patients who developed AEs (p = 0.0018). Although there was no significant difference in serum levels of CXCL5, the absolute value of CXCL5 could at least be a supportive marker for the increased absolute levels of serum sCD163. This study suggests that sCD163 and CXCL5 may serve as possible prognostic biomarkers for irAEs in patients with advanced melanoma treated with nivolumab.

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Section: Discussionmentioning

confidence: 99%

Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study

et al. 2018

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“…21 Additional hematologic markers of systemic inflammation include the PLR 17,18 19,20 A recent retrospective study of 101 patients with melanoma treated with nivolumab reported that an increased total white blood cell count and decreased lymphocyte count were associated with irAEs. 33 However, the ability of these tests to predict the occurrence of irAEs is unknown. In our study, baseline NLR, ALI, and PLR were not associated with an increased risk of irAE or pneumonitis.…”

Section: Dwight H Owen Et Almentioning

confidence: 99%

Incidence, Risk Factors, and Effect on Survival of Immune-related Adverse Events in Patients With Non–Small-cell Lung Cancer

Owen

Wei

Bertino

et al. 2018

Clinical Lung Cancer

112

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“…A recent study out of Japan has proposed the possibility of using routine blood counts as a biomarker of grade 3/4 or lung and gastrointestinal irAEs based on univariate and multivariate analysis of fluctuations in blood counts in melanoma patients receiving nivolumab. 95 This strategy may have merit as an etiology-independent, nonspecific sign of irAEs. However, the multicenter Japanese study focused on changes in blood counts that occurred during an event as compared to baseline measures before treatment.…”

Section: Etiology Of Iraes Revisitedmentioning

confidence: 99%

Clinical features, predictive correlates, and pathophysiology of immune-related adverse events in immune checkpoint inhibitor treatments in cancer: a short review

Yoest

2017

ITT

132

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Identification and characterization of T-cell regulatory mechanisms, or checkpoints, have led to a wave of drug development aimed at inhibiting these targets to “remove the brakes” of the immune system. This class of anticancer therapeutics, termed immune checkpoint inhibitors (ICIs), has harnessed the potential of the body’s own immune system to recognize cancerous cells and selectively eliminate them, in some cases with alarming success. This new breakthrough, however, has not been without its drawbacks. Immune-related adverse events (irAEs) are adverse events encountered during treatment with ICIs that are thought to be mediated through the patient’s immune system which can manifest with a variety of symptoms which often resemble autoimmunity. These events range widely in presentation and severity and are reported frequently. Here, we will discuss a large selection of case reports in order to inform the clinician, laboratorian, and researcher of the scope of organ systems affected, the severity of the conditions being encountered, and the responses of these events to treatment, as well as explore the use of ICIs in the setting of preexisting autoimmunity. We will also consider the ability to detect autoantibodies before and during irAEs as well as the correlations that irAEs have with clinical outcomes. Finally, we will conclude by exploring the possibility that two distinct pathways may be contributing to the phenomenon of irAEs within this class of drugs, and the role that this might play in future research and clinical practice.

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Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab

Cited by 82 publications

References 32 publications

Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study

Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study

Incidence, Risk Factors, and Effect on Survival of Immune-related Adverse Events in Patients With Non–Small-cell Lung Cancer

Clinical features, predictive correlates, and pathophysiology of immune-related adverse events in immune checkpoint inhibitor treatments in cancer: a short review

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