Correlation Between Immune-related Adverse Event (IRAE) Occurrence and Clinical Outcome in Patients With Metastatic Renal Cell Carcinoma (mRCC) Treated With Nivolumab: IRAENE Trial, an Italian Multi-institutional Retrospective Study

Vitale, Maria Giuseppa; Pipitone, Stefania; Venturelli, Marta; Baldessari, Cinzia; Porta, Camillo; Iannuzzi, Federica; Basso, Umberto; Scagliarini, Sarah; Zucali, Paolo Andrea; Galli, Luca; Rossetti, Sabrina; Caserta, Claudia; Bracarda, Sergio; Iacovelli, Roberto; Masini, Cristina; Cortellini, Alessio; Girolamo, Stefania Di; Buti, Sebastiano; Fornarini, Giuseppe; Carrozza, Francesco; Santoni, Matteo; Caputo, Francesco; Giaquinta, S.; Balduzzi, Sara; D’Amico, Roberto; Vitale, Giovanna; Mighali, Pasquale; Sabbatini, Roberto

doi:10.1016/j.clgc.2020.05.010

Cited by 15 publications

(5 citation statements)

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“…Accumulating evidence suggests that the increased occurrence of irAEs is associated with durable therapeutic responses with ICIs (20)(21)(22)(23)(24)(25)(26)(27)(28)(29). This association has also been independently observed in mRCC (30)(31)(32)(33)(34)(35). The current case adds support to the literature, suggesting that patients with severe multiorgan irAEs may have improved response to ICI therapy.…”

Section: Discussionsupporting

confidence: 75%

Nivolumab plus ipilimumab induced endocrinopathy and acute interstitial nephritis in metastatic sarcomatoid renal-cell carcinoma: A case report and review of literature

et al. 2022

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The prognosis of sarcomatoid renal cell carcinoma has changed dramatically with the emergence of immune checkpoint inhibitors. Notably the use of nivolumab and ipilimumab combination therapy has demonstrated promising durable therapeutic response for patients with treatment-naïve sarcomatoid renal-cell carcinoma. We present a case of 45-year-old man with a history of metastatic sarcomatoid renal cell carcinoma treated with nivolumab plus ipilimumab who developed type 1 diabetes mellitus, adrenal insufficiency, thyroiditis/hypothyroidism, and acute interstitial nephritis as a result of immunotherapy.

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Section: Discussionsupporting

confidence: 75%

Nivolumab plus ipilimumab induced endocrinopathy and acute interstitial nephritis in metastatic sarcomatoid renal-cell carcinoma: A case report and review of literature

et al. 2022

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“…One study of patients without melanoma treated with PD‐1 inhibitors found that irAEs were significantly associated with overall response rate [17]. A recent retrospective study of 167 patients with mRCC treated with nivolumab found that irAEs were associated with improved OS and PFS and higher response rates [18]. It should be noted, however, that these authors did not investigate the association of different sites of irAEs on clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Adverse Events as Clinical Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

et al. 2021

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Background. Immune checkpoint inhibitors (ICI) are an important treatment for metastatic renal cell carcinoma (mRCC). These agents may cause immune-related adverse events (irAEs) and the relationship between irAEs and outcomes is poorly understood. We investigated the association between irAEs and clinical outcomes in ICI-treated mRCC patients. Methods. We performed a retrospective study of 200 ICItreated mRCC patients at Winship Cancer Institute from 2015-2020. Data on irAEs were collected from clinic notes and laboratory values and grades were determined using common terminology criteria in adverse events (CTCAE) version 5.0. The association with overall survival (OS) and progression-free survival (PFS) was modeled by Cox proportional hazards model. Logistic regression models were used to define odds ratios for clinical benefit (CB). Landmark analysis and extended Cox models were used to mitigate lead-time bias by treating irAEs as a time-varying covariate. Results. Most patients (71.0%) were males and one-third of patients (33.0%) experienced ≥1 irAE, most commonly involving the endocrine glands (13.0%), gastrointestinal tract (10.5%), or skin (10.0%). Patients who experienced irAEs had significantly longer OS (HR=0.52, p=0.013), higher chance of CB (OR=2.10, p=0.023) and showed a trend towards longer PFS (HR=0.71, p=0.065) in multivariate analysis. Patients who had endocrine irAEs, particularly thyroid irAEs, had significantly longer OS, PFS, and higher chance of CB. In 14-week landmark analysis, irAEs were significantly associated with prolonged OS (p=0.045). Patients who experienced irAEs had significantly longer median OS (44.5 versus 18.2 months, p=0.005) and PFS (7.5 versus 3.6 months, p=0.003) without landmark compared to patients who did not. Conclusions. We found that ICI-treated mRCC patients who experienced irAEs, particularly thyroid irAEs, had significantly improved clinical outcomes compared to patients who did not have irAEs. This suggests that irAEs may be effective clinical biomarkers in ICI-treated mRCC patients. Future, prospective studies are warranted to validate these findings. The Oncologist 2021;9999:• •

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“…The present study found no significant relationship between the number of irAE, including dermatological irAE, and the survival parameters (OS and PFS). An association between these two parameters has been reported in cohort studies including melanoma and other patients with cancer [38–43] but remains controversial. This discrepancy might be due to a dilution of the association in the present study including all class of ICI and not only anti‐PD1 therapy.…”

Section: Discussionmentioning

confidence: 99%

Association between immune‐related adverse events and prognosis in patients treated with immune checkpoint inhibitors in melanoma: A surrogacy analysis

Euvrard,

Robert,

Mainbourg

et al. 2023

Fundamemntal Clinical Pharma

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BackgroundImmune checkpoint inhibitors (ICI) represent a breakthrough in oncology in terms of prognosis and safety. They now constitute a cornerstone in the management of metastatic melanoma. However, a new kind of adverse event called immune‐related adverse events (irAE) has emerged. These irAE could be conceptually considered as an indicator of the antitumoral immune response, but the association between irAE and prognosis is still a matter of debate.ObjectiveThe purpose of this study was to investigate the association between the overall survival (OS) and the prevalence of irAE in melanoma.MethodsMEDLINE/PubMed, WebofScience, ClinicalTrials, and WHOTrials databases were searched to identify phase 3 randomized controlled trials (RCT) assessing ICI in melanoma and published up to April 2021. A weighted regression was performed to estimate this association according to standard method of surrogacy analysis.ResultsA total of 14 RCT including 7646 patients (median age: 59.3 years) with melanoma were included. All types of ICI were represented (ipilimumab, tremelimumab, pembrolizumab, nivolumab, atezolizumab, as well as ipilimumab and nivolumab combination). irAE were frequent but rarely fatal. The combination of ICI caused more irAE than anti‐PD1 (or PDL1) and anti‐CTLA4 monotherapies. No relationship was found between the occurrence of irAE and OS (beta coefficient 0.078, R2 3%, p = 0.52), nor between cutaneous irAE and OS (beta coefficient 0.080, R2 6%, p = 0.33).ConclusionAlthough limited by the heterogeneity of ICI included in the regression and the low number of included RCT, the present study suggests an absence of association between irAE and prognosis in melanoma.

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Correlation Between Immune-related Adverse Event (IRAE) Occurrence and Clinical Outcome in Patients With Metastatic Renal Cell Carcinoma (mRCC) Treated With Nivolumab: IRAENE Trial, an Italian Multi-institutional Retrospective Study

Cited by 15 publications

References 37 publications

Nivolumab plus ipilimumab induced endocrinopathy and acute interstitial nephritis in metastatic sarcomatoid renal-cell carcinoma: A case report and review of literature

Nivolumab plus ipilimumab induced endocrinopathy and acute interstitial nephritis in metastatic sarcomatoid renal-cell carcinoma: A case report and review of literature

Immune-Related Adverse Events as Clinical Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

Association between immune‐related adverse events and prognosis in patients treated with immune checkpoint inhibitors in melanoma: A surrogacy analysis

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