The impact of sarcopenia on the efficacy and safety of immune checkpoint inhibitors in patients with solid tumours

Haik, Laura; Gonthier, Aurore; Quivy, Amandine; Gross‐Goupil, Marine; Veillon, Rémi; Frison, Éric; Ravaud, Alain; Domblides, Charlotte; Daste, Amaury

doi:10.1080/0284186x.2021.1978540

Cited by 13 publications

(21 citation statements)

References 40 publications

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“…In our statistical analysis, sarcopenia was not a significant factor for predicting irAEs, which was similar to our previous report ( 40 ) and other studies ( 16 , 18 , 27 ). However, previous study found that patients with sarcopenia experienced significantly increased risk of irAEs ( 22 , 41 ).…”

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

“…Previously, several studies have attempted to investigate the potential impact of sarcopenia on the efficacy of ICIs, but with inconsistent results (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). These results cannot be directly compared, for their different inclusion criteria, different definition of sarcopenia [total cross-skeletal muscle (16-18, 21-25, 27, 29) vs. psoas muscle area (19,20,26,28)], or different methods for measuring muscle mass [CT (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) vs. DXA (30)]. In addition, the majority of studies enrolled patients receiving second or more treatment lines ICIs, while only three studies enrolled a small proportion [13.4% (23), 16.5% (17), and 38.3% (30), respectively] of patients receiving ICIs as first-line treatment.…”

Section: Introductionmentioning

confidence: 99%

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Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors

Liu

Ren

et al. 2022

Front. Nutr.

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BackgroundIt remains not well known whether skeletal muscle mass (SMM) loss has any impact on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer. We aimed to evaluate the association between SMM and clinical outcome of patients with advanced lung cancer receiving ICIs as first line or second line.Materials and MethodsFrom March 1st, 2019 to March 31st, 2021 at our hospital, 34 patients with advanced lung cancer treated with first-line or second-line ICIs were enrolled retrospectively. The estimation of skeletal muscle index (SMI) for sarcopenia was assessed at the level of the third lumbar vertebra (L3) on computed tomography (CT) images obtained within 4 weeks before initiation of ICIs treatment. The impact of sarcopenia (low SMI) on progression free survival (PFS) was analyzed using Kaplan-Meier method and log-rank tests. The effect of various variables on PFS was evaluated using Cox proportional hazards regression model with univariate and multivariate analysis. The impact on treatment response including objective response rate (ORR) and disease control rate (DCR) and immunotherapy related adverse events (irAEs) between patients with and without sarcopenia was compared by the chi-squared test. The comparison of SMI value between patients with objective response (OR), disease control (DC) and those without OR and DC was used student t-test or Mann-Whitney U test.ResultsBoth in univariate and multivariate analysis, sarcopenia and treatment lines were the predictive factors for PFS (p < 0.05). Patients with sarcopenia had significantly shorter PFS than that of non-sarcopenic ones [6.57 vs. 16.2 months, hazard ratios (HR) = 2.947 and 3.542, and 95% confidence interval (CI): 1.123–13.183 and 1.11–11.308, p = 0.022 and 0.033]. No significant difference in ORR and irAEs was found. Patients with sarcopenia had lower DCR than those without sarcopenia. The mean SMI value of DCR group and non-DCR group was 32.94 ± 5.49 and 44.77 ± 9.06 cm2/m2, respectively (p = 0.008).ConclusionSarcopenia before immunotherapy might be a significant predictor for poor prognosis including shorter PFS and lower DCR in patients with advanced lung cancer treated with ICIs as first line or second line.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors

Liu

Ren

et al. 2022

Front. Nutr.

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“…As we mentioned in the Introduction section, no association between sarcopenia and prognosis in patients with ATZ/BEV therapy has been reported. In other cancer types, there are reports that sarcopenia leads to worse prognosis in patients with ICI therapy, 14,23 but others show that it has no effect on prognosis 24,25 . There are differences in the molecular mechanisms among carcinomas, and in sarcopenia, in particular, there are reports of associations with the patient's immune status and other factors.…”

Section: Discussionmentioning

confidence: 99%

“…In other cancer types, there are reports that sarcopenia leads to worse prognosis in patients with ICI therapy, 14 , 23 but others show that it has no effect on prognosis. 24 , 25 There are differences in the molecular mechanisms among carcinomas, and in sarcopenia, in particular, there are reports of associations with the patient's immune status and other factors. Thus, large‐scale studies and exploration of biomarkers associated with sarcopenia in HCC patients with ATZ/BEV therapy are needed in the future.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the prognostic effect of sarcopenia on atezolizumab plus bevacizumab and lenvatinib therapy in hepatocellular carcinoma patients

et al. 2022

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Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach

Botticelli

Cirillo

Pomati

et al. 2023

Cancer Immunol Immunother

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Background Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development. Methods A prospective, multicenter study evaluating the immune profile (IP) of 79 patients with advanced cancer and treated with anti-programmed cell death protein 1 (anti-PD-1) drugs as a first- or second-line setting was performed. The results were then correlated with irAEs onset. The IP was studied by means of multiplex assay, evaluating circulating concentration of 12 cytokines, 5 chemokines, 13 soluble immune checkpoints and 3 adhesion molecules. Indoleamine 2, 3-dioxygenase (IDO) activity was measured through a modified liquid chromatography–tandem mass spectrometry using the high-performance liquid chromatography-mass spectrometry (HPLC–MS/MS) method. A connectivity heatmap was obtained by calculating Spearman correlation coefficients. Two different networks of connectivity were constructed, based on the toxicity profile. Results Toxicity was predominantly of low/moderate grade. High-grade irAEs were relatively rare, while cumulative toxicity was high (35%). Positive and statistically significant correlations between the cumulative toxicity and IP10 and IL8, sLAG3, sPD-L2, sHVEM, sCD137, sCD27 and sICAM-1 serum concentration were found. Moreover, patients who experienced irAEs had a markedly different connectivity pattern, characterized by disruption of most of the paired connections between cytokines, chemokines and connections of sCD137, sCD27 and sCD28, while sPDL-2 pair-wise connectivity values seemed to be intensified. Network connectivity analysis identified a total of 187 statistically significant interactions in patients without toxicity and a total of 126 statistically significant interactions in patients with toxicity. Ninety-eight interactions were common to both networks, while 29 were specifically observed in patients who experienced toxicity. Conclusions A particular, common pattern of immune dysregulation was defined in patients developing irAEs. This immune serological profile, if confirmed in a larger patient population, could lead to the design of a personalized therapeutic strategy in order to prevent, monitor and treat irAEs at an early stage.

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The impact of sarcopenia on the efficacy and safety of immune checkpoint inhibitors in patients with solid tumours

Cited by 13 publications

References 40 publications

Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors

Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors

Comparison of the prognostic effect of sarcopenia on atezolizumab plus bevacizumab and lenvatinib therapy in hepatocellular carcinoma patients

Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach

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