Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients

Cortellini, Alessio; Chiari, Rita; Ricciuti, Biagio; Metro, Giulio; Perrone, Fabiana; Tiseo, Marcello; Bersanelli, Melissa; Bordi, Paola; Santini, Daniele; Giusti, Raffaele; Grassadonia, Antonino; Marino, Pietro Di; Tinari, Nicola; Tursi, Michele De; Zoratto, Federica; Veltri, Enzo; Malorgio, Francesco; Garufi, Carlo; Russano, Marco; Anesi, Cecilia; Zeppola, Tea; Filetti, Marco; Marchetti, Paolo; Berardi, Rossana; Rinaldi, Silvia; Tudini, Marianna; Silva, Rosa Rita; Pireddu, Annagrazia; Atzori, Francesco; Iacono, Daniela; Migliorino, Maria Rita; Porzio, Giampiero; Cannita, Katia; Ficorella, Corrado; Buti, Sebastiano

doi:10.1016/j.cllc.2019.02.006

Cited by 134 publications

(145 citation statements)

References 26 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…Even if sarcopenia has been associated with a greater incidence of chemotherapy toxicity 1 , things might be different with the irAEs. Recent findings suggest that being a pharmacodynamic resultance, the occurence of irAEs could be considered a biomarker of immunotherapy efficacy across different tumor tipes [25][26][27][28] . From this perspective, patients who are likely to benefit more from ICIs treatments, should be the same who are more likely to experience irAEs, so we might speculate that with ICIs, sarcopenic patients should experience less irAEs compared to non-sarcopenic patients.…”

Section: Overallmentioning

confidence: 99%

“…Recently, an interesting study have tried to shed a light on the complex inter-relations between sex, BMI and sarcopenia, in melanoma patients treated with ICIs (using serum creatinine as a surrogate of muscle mass) 35 . The authors intriguingly found that the best clinical outcome is achieved in overweight/class I obese patients (BMI [25][26][27][28][29][30][31][32][33][34][35], particularly among males, who had higher serum creatinine levels (which stands for a good muscle mass) 35 . BMI and muscle mass seem to have a direct proportionality (the higher is the BMI, the higher the SMI), vice versa their effect on immunotherapy clinical outcomes appears opposite (high BMI has a positive predictive and prognostic role, while sarcopenia has a negative prognostic role), which overlaps in a specific subset of patients (overweight non sarcopenic).…”

Section: Overallmentioning

confidence: 99%

See 1 more Smart Citation

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Cortellini

Bozzetti

Palumbo

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/−25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p = 0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR = 1.66 [95% CI: 1.05-2.61]; p = 0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR = 2.19 [95% CI: 1.31-3.64]; p = 0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR = 2.19 [1.31-3.67]; p = 0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.Sarcopenia is the condition of loss of muscle mass, with decreased muscle power, and it is one of the hallmarks of cancer, which negatively affects the most of clinical outcomes such as toxicities and survival 1 . The interactions must recognize also the lack of other adiposity metrics, such as the waist circumference, the waist-to-height ratio, and the body fat percentage. Moreover, the CT imaging analysis was limited by the data availability; indeed, the acquisition protocol was planned according to the presence of previous examination. conclusionOur finding of a significant shorter OS for low-SMI patients treated with PD-1/PD-L1 checkpoint inhibitors, suggests that sarcopenia might have a prognostic role, rather than predictive. However, to properly weighing our results, we must consider the significant association between poorer PS and low-SMI. Without making conclusive considerations, we can assume that after the advent of ICIs, we should give back further relevance to baseline nut...

show abstract

Section: Overallmentioning

confidence: 99%

Section: Overallmentioning

confidence: 99%

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Cortellini

Bozzetti

Palumbo

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…The largest study focused on the association of irAEs with ICI treatment efficacy to date was recently conducted by Cortellini et al (40). Their retrospective study included 559 patients with advanced NSCLC treated with nivolumab or pembrolizumab (40). The results of a multivariate analysis showed a higher ORR was related to experiencing any irAE (p<0.0001), and endocrine (p=0.0043) and skin (p=0.0005) irAEs; significantly longer PFS was associated with irAEs of any grade (p<0.0001), endocrine (p=0.0084) and skin (p=0.0001); and significantly longer OS was associated with irAEs of any grade (p<0.0001), endocrine (p=0.0044), gastrointestinal (p=0.0437), and skin (p=0.0006) irAEs.…”

Section: Iraes and Outcome In Nsclcmentioning

confidence: 99%

“…The results of a multivariate analysis showed a higher ORR was related to experiencing any irAE (p<0.0001), and endocrine (p=0.0043) and skin (p=0.0005) irAEs; significantly longer PFS was associated with irAEs of any grade (p<0.0001), endocrine (p=0.0084) and skin (p=0.0001); and significantly longer OS was associated with irAEs of any grade (p<0.0001), endocrine (p=0.0044), gastrointestinal (p=0.0437), and skin (p=0.0006) irAEs. The 6-weeks landmark analysis revealed irAEs of any grade as an independent predictive factor for higher ORR, and longer PFS and OS (40). The results of selected studies on patients with NSCLC are summarised in Table II.…”

Section: Iraes and Outcome In Nsclcmentioning

confidence: 99%

Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Enterocolitis , hypophysitis and thyroid dysfunction have reportedly been associated with anti‐tumour response or improved outcome. Beyond melanoma, a study of 559 patients with NSCLC reported an increased overall response rate (ORR), PFS and OS in patients with any‐grade irAEs compared to those without at multivariate analysis .…”

Section: Toxicity Of Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Mechanisms of checkpoint inhibition-induced adverse events

Urwyler

Earnshaw

Bermudez

et al. 2020

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Immune checkpoint inhibition has revolutionized the treatment of several solid cancers, most notably melanoma and non-small-cell lung cancer (NSCLC). Drugs targeting cytotoxic T lymphocyte antigen (CTLA)-4 and programmed cell death 1 (PD-1) have made their way into routine clinical use; however, this has not been without difficulties. Stimulation of the immune system to target cancer has been found to result in a reduction of self-tolerance, leading to the development of adverse effects that resemble autoimmunity. These adverse effects are erratic in their onset and severity and can theoretically affect any organ type. Several mechanisms for immunerelated toxicity have been investigated over recent years; however, no consensus on the cause or prediction of toxicity has been reached. This review seeks to examine reported evidence for possible mechanisms of toxicity, methods for prediction of those at risk and a discussion of future prospects within the field.

show abstract

Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients

Cited by 134 publications

References 26 publications

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

Mechanisms of checkpoint inhibition-induced adverse events

Contact Info

Product

Resources

About