Immune-related adverse events from combination immunotherapy in cancer patients: A comprehensive meta-analysis of randomized controlled trials

Zhang, Bo; Wu, Qiong; Zhou, You; Guo, Xinyu; Ge, Jun; Fu, Jiaji

doi:10.1016/j.intimp.2018.08.014

Cited by 80 publications

(62 citation statements)

References 46 publications

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“…In contrast, the most frequent potential irAEs of anti-PD-1 therapies involved the endocrine system (hypothyroidism, hyperthyroidism, thyroiditis, and adrenal insufficiency), gastrointestinal tract (pancreatitis and peritonitis), hepatobiliary system (hepatitis, and hepatocellular injury), endocrine system (diabetes mellitus, diabetic ketoacidosis, hyperglycemia, and type 1 diabetes mellitus), musculoskeletal system (arthritis, myalgia, and myositis), nervous system (Guillain-Barre syndrome), renal system (acute renal failure, and renal failure), and respiratory system (pneumonitis). Our finding that the combination of anti-CTLA-4 and anti-PD-1 therapies resulted in a frequent incidence of potential irAEs is consistent with the findings of three published reviews (63)(64)(65). The point estimates of the incidence of the potential irAEs in our study were slightly different from those obtained in previous meta-analyses because of different inclusion criteria; specifically, including phase1-3 ICI trials in advanced melanoma.…”

Section: Discussionsupporting

confidence: 80%

Potential Immune-Related Adverse Events Associated With Monotherapy and Combination Therapy of Ipilimumab, Nivolumab, and Pembrolizumab for Advanced Melanoma: A Systematic Review and Meta-Analysis

et al. 2020

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Background: The use of ipilimumab, nivolumab, and pembrolizumab as monotherapies or in combination has transformed the management of advanced melanoma even though these drugs are associated with a new profile of immune-related adverse events (irAEs). The incidence of irAEs from clinical trials of these agents is an important factor for clinicians when treating patients with advanced melanoma. In the current study, we aimed to profile the incidence of potential irAEs of these agents when used as monotherapy and as combination therapy. Methods: We searched the Medline, Embase, and Cochrane databases; clinicaltrials.gov; and websites of regulatory agencies in the USA, Europe, Australia, and Japan for phase 1-3 trials of ipilimumab, nivolumab, and pembrolizumab for advanced melanoma. Random effect meta-analysis was utilized to profile the incidence of potential irAEs. Results: A total of 58 reports of 35 trials including 6,331 patients with advanced melanoma and reporting irAE data were included in the meta-analyses. We found higher incidences of potential irAEs in combination therapies vs. monotherapies for most of the types of irAEs. Among the monotherapies, ipilimumab users had the most frequent incidence of potential irAEs related to the gastrointestinal system (diarrhea, 29%; and colitis, 8%) and skin (rash, 31%; pruritus, 27%; and dermatitis, 10%), with hypophysitis in 4% of the patients. The most frequent potential irAEs among nivolumab users were maculopapular rash (13%), erythema (4%), hepatitis (3%), and infusion-related reactions (3%), while they were arthralgia (12%), hypothyroidism (8%), and hyperglycemia (6%), among pembrolizumab users. Almutairi et al. Immune-Related Adverse Events of Immunotherapies in Melanoma Conclusion: Especially the combination therapies tend to elevate the incidence of potential irAEs. Clinicians should be vigilant about irAEs following combination therapy as well as gastrointestinal and skin irAEs following ipilimumab therapy, in addition to being aware of potential irAEs leading to hyperglycemia, thyroid, hepatic, and musculoskeletal disorders following nivolumab and pembrolizumab therapy.

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Section: Discussionsupporting

confidence: 80%

Potential Immune-Related Adverse Events Associated With Monotherapy and Combination Therapy of Ipilimumab, Nivolumab, and Pembrolizumab for Advanced Melanoma: A Systematic Review and Meta-Analysis

et al. 2020

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“…Our findings suggest that the frequency of severe irAE‐N may be higher than what has been reported in the published clinical trials. Not surprisingly, the current study redemonstrated that combination anti–CTLA‐4 plus anti–PD‐1/PD‐L therapy and anti–CTLA‐4 therapy monotherapy is associated with a higher risk of irAE‐N compared to anti–PD‐1/PD‐L1 monotherapy . In another systematic review and meta‐analysis of 36 comparative phase II and III randomized trials evaluating safety profiles of different ICIs, atezolizumab had the lowest probability of grade ≥ 3 adverse events .…”

Section: Frequency Of Severe Irae‐n and Associated Ici Classessupporting

confidence: 50%

Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum

Dubey

David

Reynolds

et al. 2020

Annals of Neurology

168

189

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Expanding use of immune-checkpoint inhibitors (ICIs) underscores the importance of accurate diagnosis and timely management of neurological immune-related adverse events (irAE-N). We evaluate the real-world frequency, phenotypes, co-occurring immune-related adverse events (irAEs), and long-term outcomes of severe, grade III to V irAE-N at a tertiary care center over 6 years. We analyze how our experience supports published literature and professional society guidelines. We also discuss these data with regard to common clinical scenarios, such as combination therapy, ICI rechallenge and risk of relapse of irAE-N, and corticosteroid taper, which are not specifically addressed by current guidelines and/or have limited data. Recommendations for management and future irAE-N reporting are outlined.

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“…The incidence rates of any grade and grade 3 or higher irAEs were 88% and 41%, respectively. 34 Myocarditis, myositis, and neurologic events are the most common fatal ICI toxic events in this combination strategy. 32…”

Section: Iraes In Patients With Cancermentioning

confidence: 99%

<p>Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma</p>

Cui¹,

Liu²,

Wang³

et al. 2020

OTT

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Immune-related adverse events from combination immunotherapy in cancer patients: A comprehensive meta-analysis of randomized controlled trials

Cited by 80 publications

References 46 publications

Potential Immune-Related Adverse Events Associated With Monotherapy and Combination Therapy of Ipilimumab, Nivolumab, and Pembrolizumab for Advanced Melanoma: A Systematic Review and Meta-Analysis

Potential Immune-Related Adverse Events Associated With Monotherapy and Combination Therapy of Ipilimumab, Nivolumab, and Pembrolizumab for Advanced Melanoma: A Systematic Review and Meta-Analysis

Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum

<p>Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma</p>

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