The 2016–2019 ImmunoTOX assessment board report of collaborative management of immune-related adverse events, an observational clinical study

Michot, Jean‐Marie; Lappara, Ariane; Pavec, Jérôme Le; Simonaggio, Audrey; Collins, Michael; Martin, Eléonora De; Danlos, François‐Xavier; Ammari, Samy; Cauquil, Cécile; Éderhy, Stéphane; Barreau, Emmanuel; Belkhir, Rakiba; Berdelou, A.; Lazarovici, Julien; Chanson, Philippe; Izzedine, Hassan; Seferian, Andrei; Pajolec, Christine Le; Baldini, Capucine; Martín-Romano, Patricia; Mariette, Xavier; Robert, Caroline; Besse, Benjamin; Hollebecque, Antoine; Varga, Andréa; Laghouati, Salim; Mateus, Christine; Voisin, Anne-Laure; Soria, Jean‐Charles; Massard, Christophe; Marabelle, Aurélien; Champiat, Stéphane; Lambotte, Olivier

doi:10.1016/j.ejca.2020.02.010

Cited by 44 publications

(17 citation statements)

References 28 publications

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“…The decision to rechallenge was taken by the referent oncologist after a thorough evaluation of the individual risk/benefit imbalance and pluridisciplinary concentration in the setting of the assessment board iTOX. 18 Importantly, all patients had initial CTCAE grade II-III n-irAEs which improved either spontaneously (patients #14 and patient # 39) or after corticosteroid therapy (patients #21, #24 and #27), and with only mild sequelae at the time of rechallenge for 3/5 (patients #14, #27 and #39). Four of the five patients resumed their initial immunotherapy (i.e.…”

Section: Resultsmentioning

confidence: 98%

Neurological complications induced by immune checkpoint inhibitors: a comprehensive descriptive case-series unravelling high risk of long-term sequelae

Plaçais

Michot

Champiat

et al. 2021

Brain Communications

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Neurological immune-related adverse events (n-irAEs) are complications of programmed-cell death 1 (anti-PD-1) or programmed-cell death 1 ligand (anti-PD-L1) immunotherapies that can be life threatening and often lead to anticancer immunotherapy withdrawal. Scant clinical data are available that integrate the clinical presentation, therapeutic management, and long-term outcome. All consecutive adult patients treated by programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies, given alone or in combination with other treatment, who experienced a neurological immune-related adverse event with a severity grade ≥ 2 in Paris Saclay-University hospitals were investigated from June 2014 to February 2019. The frequency of neurological immune-related adverse events was calculated from the prospective Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC) cohort. Forty patients presenting with 51 distinct neurological immune-related adverse events were included. The prevalence of grade ≥ 2 neurological immune-related adverse events was estimated to be 1.22% in the Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Among 40 patients with neurological immune-related adverse events, 65% received programmed-cell death 1 or programmed-cell death 1 ligand monotherapy and 35% received a combination of programmed-cell death 1 plus anti-CTLA4 (Common Terminology Criteria for Adverse Events). Clinical neurological presentations were peripheral (48%), central (35%), or mixed (18%). The severity of neurological immune-related adverse events were grade 2 for 14 (35%) and ≥ grade 3 for 26 patients (65%). The mortality rate related to neurological immune-related adverse events was 8%. Corticosteroid treatment led to neurological recovery in 74%. Long-term follow-up highlighted that 53% of patients experienced long-term neurological sequelae. Five patients were rechallenged by programmed-cell death 1 monotherapy without recurrence of their neurological immune-related adverse event(s). Neurological immune-related adverse events induced by programmed-cell death 1 or programmed-cell death 1 ligand are rare but are severe with a mortality rate of 8% and long-term sequelae for 53% of patients. Corticosteroids should be started when neurological immunological complications are identified to avoid long-term sequelae.

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Section: Resultsmentioning

confidence: 98%

Neurological complications induced by immune checkpoint inhibitors: a comprehensive descriptive case-series unravelling high risk of long-term sequelae

Plaçais

Michot

Champiat

et al. 2021

Brain Communications

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“…We conducted a retrospective multicentric study including patients from 4 French university hospitals in Paris area. All centers were oncologic centers and were organized with a multidisciplinary board [27] to discuss the management of immune-related adverse events. Patients eligible were admitted to ICUs between January 2013 and October 2019, during the course of an ICI treatment (either anti-PD-1 (NIVOLUMAB, PEMBROLIZUMAB or SPARTALIZUMAB), anti-PDL-1 (ATEZOLIZUMAB, DURVALUMAB), anti-CTLA4 (IPILIMUMAB or TREMELIMUMAB) or a combination of ICI.…”

Section: Methodsmentioning

confidence: 99%

“…Patients were then classified according to the reason for admission, whether related to an immune-related adverse event (irAE), an intercurrent adverse event not related to immunotherapy (intE) or a complication related to tumor progression (TumProg). Imputability of the ICI for irAEs was assessed by the physician in charge, discussed in multidisciplinary boards in most cases [ 27 ] and reviewed by investigators (AJ and VL), according to the World Health Organization Uppsala Monitoring Centre scale for standardized case causality assessment and organ-specific guidelines when available [ 16 ]. Tumor progression was defined as peri-tumoral hemorrhage, tumor obstruction or lymphangitis carcinomatosis.…”

Section: Methodsmentioning

confidence: 99%

Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit

Joseph

Simonaggio

Stoclin

et al. 2020

Ann. Intensive Care

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Background Immune checkpoint inhibitors have reshaped the standard of care in oncology. However, they have been associated with potentially life-threatening immune-related adverse events. With the growing indications of immune checkpoint inhibitors and their position as a pillar of cancer treatment, intensive care physicians will be increasingly confronted with their side effects. The outcome of patients with severe immune-related adverse events in the intensive care unit remains unknown. This retrospective multicentric study aims to describe the characteristics of patients admitted to the intensive care units of 4 academic hospitals in Paris area while receiving immune checkpoint inhibitor treatment between January 2013 and October 2019. Results Over the study period, 112 cancer patients who received immune checkpoint inhibitors were admitted to the intensive care unit within 60 days after the last dose. ICU admission was related to immune-related adverse events (n = 29, 26%), other intercurrent events (n = 39, 35%), or complications related to tumor progression (n = 44, 39%). Immune-related adverse events were pneumonitis (n = 8), colitis (n = 4), myocarditis (n = 3), metabolic disorders related to diabetes (n = 3), hypophysitis (n = 2), nephritis (n = 2), meningitis or encephalitis (n = 2), hepatitis (n = 2), anaphylaxis (n = 2) and pericarditis (n = 1). Primary tumors were mostly melanomas (n = 14, 48%), non-small-cell lung cancers (n = 7, 24%), and urothelial carcinomas (n = 5, 17%). Diagnosis of melanoma and a neutrophil/lymphocyte ratio < 10 were associated with immune-related diagnosis versus other reasons for ICU admission. During their ICU stay, immune-related adverse events patients needed vasopressors (n = 7), mechanical ventilation (n = 6), and extra-corporeal membrane oxygenation (n = 2). One-year survival was significantly higher for patients admitted for irAE compared to patients admitted for other reasons (p = 0.004). Conclusions Admission to the intensive care unit related to immune-related adverse event was associated with better outcome in cancer patients treated with immune checkpoint inhibitors. Our results support the admission for an intensive care unit trial for patients with suspected immune-related adverse events.

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“…We believe that the management of ICI-induced liver toxicity should be guided by multidisciplinary discussions involving different specialists such as oncologists, hepatologists, immunologists, radiologists and pathologists. 114 Impact of corticosteroids on the response to immunotherapy It appears that using systemic corticosteroids or a second-line immunosuppressive drug did not significantly impact overall survival (OS) during several clinical trials. 115 It has been reported quite recently that patients who experienced severe irAEs (grade > − 3) may even have an improved overall response rate and longer median time to progression compared to those without grade > − 3 irAEs, despite the use of corticosteroids.…”

Section: Proposed Management Algorithmmentioning

confidence: 99%

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

et al. 2020

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Immune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

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The 2016–2019 ImmunoTOX assessment board report of collaborative management of immune-related adverse events, an observational clinical study

Cited by 44 publications

References 28 publications

Neurological complications induced by immune checkpoint inhibitors: a comprehensive descriptive case-series unravelling high risk of long-term sequelae

Neurological complications induced by immune checkpoint inhibitors: a comprehensive descriptive case-series unravelling high risk of long-term sequelae

Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

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