Correlation between blood cell count and outcome of melanoma patients treated with anti-PD-1 antibodies

Nakamura, Yoshiyuki; Tanaka, Ryota; Maruyama, Hiroshi; Ishitsuka, Yosuke; Okiyama, Naoko; Watanabe, Rei; Fujimoto, Manabu; Fujisawa, Yasuhiro

doi:10.1093/jjco/hyy201

Cited by 75 publications

(83 citation statements)

References 28 publications

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“…Although we could analyze only a limited number of patient samples, it is speculated that occurrence of irAEs may be associated with survival even after adjusting other prognostic factors in AGC patients treated with nivolumab. Previous studies have reported that peripheral blood cell count or NLR in clinical course correlated with prognosis in several cancers [30]. However, in our study, it could not be said that these factors were useful biomarkers for predicting occurrence of irAE.…”

Section: Discussioncontrasting

confidence: 77%

Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab

et al. 2019

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BackgroundRecent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit in patients with melanoma or lung cancer. In advanced gastric cancer (AGC) patients, there have been few reports about the correlation between irAEs and efficacy of immune checkpoint inhibitors. In this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab.MethodsThe subjects of this study were AGC patients received nivolumab monotherapy between January 2015 and August 2018. IrAEs were defined as those AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy and/or endocrine therapy. We divided the patients who received nivolumab into two groups based on occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group). We assessed the efficacy in both groups.ResultsOf the 65 AGC patients that received nivolumab monotherapy, 14 developed irAEs. The median time to onset of irAEs was 30.5 days (range 3–407 days). Median follow-up period for survivors was 32 months (95% CI, 10.8 to 34.5). The median progression-free survival was 7.5 months (95% CI, 3.6 to 11.5) in the irAE group and 1.4 months (95% CI, 1.2 to 1.6) in the non-irAE group (HR = 0.11, p < 0.001). The median overall survival was 16.8 months (95% CI, 4.4 to not reached) in the irAE group and 3.2 months (95% CI, 2.2 to 4.1) in the non-irAE group (HR = 0.17, p < 0.001). Multivariate analysis demonstrated that number of metastatic sites ≥2 (HR = 2.15; 95% CI, 1.02 to 4.54), high ALP level (HR = 2.50; 95% CI, 1.27 to 4.54), and absence of irAEs (HR = 9.54, 95% CI, 3.34 to 27.30 for yes vs. no) were associated with a poor prognosis. The most frequent irAEs was diarrhea/colitis (n = 5). Grade 3 adverse events were observed in 6 patients; hyperglycemia (n = 2), diarrhea/colitis (n = 1), adrenal insufficiency (n = 1), aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). There were no grade 4 or 5 adverse events related to nivolumab.ConclusionsDevelopment of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.

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Section: Discussioncontrasting

confidence: 77%

Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab

et al. 2019

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“…[21][22][23][24][25][26] In the discovery cohort pertaining to this study, we observed a correlation between high neutrophil to lymphocyte ratio (NLR) and survival, with similar cutoff points as those described previously. 27 Flow cytometric analysis revealed that, in this patient cohort, activated NK cells inversely correlate with OS and, in the case of the early activation marker CD69, may also hold predictive value for PFS. While initially unexpected, the explanation for these results may lie within the possible immunosurveillance role that has been attributed to NK cells in controlling metastatic disease.…”

Section: Discussionmentioning

confidence: 70%

PD-1 checkpoint blockade in advanced melanoma patients: NK cells, monocytic subsets and host PD-L1 expression as predictive biomarker candidates

et al. 2020

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Blockade of the PD-1 receptor has revolutionized the treatment of metastatic melanoma, with significant increases in overall survival (OS) and a dramatic improvement in patient quality of life. Despite the success of this approach, the number of benefitting patients is limited and there is a need for predictive biomarkers as well as a deeper mechanistic analysis of the cellular populations involved in clinical responses. With the aim to find predictive biomarkers for PD-1 checkpoint blockade, an in-depth immune monitoring study was conducted in 36 advanced melanoma patients receiving pembrolizumab or nivolumab treatment at Karolinska University Hospital. Blood samples were collected before treatment and before administration of the second and fourth doses. Peripheral blood mononuclear cells were isolated and stained for flow cytometric analysis within 2 h of sample collection. Overall survival and progression-free survival (PFS) were inversely correlated with CD69 expression NK cells. In the myeloid compartment, high frequencies of non-classical monocytes and low frequencies of monocytic myeloid derived suppressor cells (MoMDSCs) correlated with response rates and OS. A deeper characterization of monocytic subsets showed that PD-L1 expression in MDSCs, non-classical and intermediate monocytes was significantly increased in patients with shorter PFS in addition to correlating inversely with OS. Our results suggest that cellular populations other than T cells can be critical in the outcome of PD-1 blockade treatment. Specifically, the frequencies of activated NK cells and monocytic subsets are inversely correlated with survival and clinical benefit, suggesting that their role as predictive biomarkers should be further evaluated.

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“…and Diehl A et al. provided evidence that in melanoma and renal carcinoma eosinophils counts was also associated to the incidence of irAEs ( 124 , 126 ).…”

Section: Systemic Biomarkers Of Iraes and Ici-induced Akimentioning

confidence: 99%

“…Systemic biomarkers of irAEs as lymphocytes and eosinophils counts, neutrophil-to-lymphocytes ratio ( 123 , 124 ), and cytokine circulating level have been assessed due to poor invasive and routine measurements.…”

Section: Systemic Biomarkers Of Iraes and Ici-induced Akimentioning

confidence: 99%

The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?

et al. 2020

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Immune checkpoint inhibitors (ICIs) are a novel class of immunotherapy drugs that have improved the treatment of a broad spectrum of cancers as metastatic melanoma, non-small lung cancer or renal cell carcinoma. These humanized monoclonal antibodies target inhibitory receptors (e.g. CTLA-4, PD-1, LAG-3, TIM-3) and ligands (PD-L1) expressed on T lymphocytes, antigen presenting cells and tumor cells and elicit an anti-tumor response by stimulating immune system. Nevertheless, the improved overall survival is complicated by the manifestation of Immune-related Adverse Effects (irAEs). During treatment with ICIs, the most common adverse kidney effect is represented by the development of acute kidney injury (AKI) with the acute tubulointerstitial nephritis as recurrent histological feature. The mechanisms involved in ICIs-induced AKI include the re-activation of effector T cells previously stimulated by nephrotoxic drugs (i.e. by antibiotics), the loss of tolerance versus self-renal antigens, the increased PD-L1 expression by tubular cells or the establishment of a pro-inflammatory milieu with the release of self-reactive antibodies. For renal transplant recipient treated with ICIs, the increased incidence of rejection is a serious concern. Therefore, the combination of ICIs with mTOR inhibitors represents an emerging strategy. Finally, it is relevant to anticipate which patients under ICIs would experience severe irAEs and from a kidney perspective, to predict patients with higher risk of AKI. Here, we provide a detailed overview of ICIs-related nephrotoxicity and the recently described multicenter studies. Several factors have been reported as biomarkers of ICIs-irAEs, in this review we speculate on potential biomarkers for ICIs-associated AKI.

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Correlation between blood cell count and outcome of melanoma patients treated with anti-PD-1 antibodies

Cited by 75 publications

References 28 publications

Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab

Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab

PD-1 checkpoint blockade in advanced melanoma patients: NK cells, monocytic subsets and host PD-L1 expression as predictive biomarker candidates

The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?

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