Dataset Information

Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis.

ABSTRACT: Importance:If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown. Objective:To compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens. Data Sources:A PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," "MDX-010," "nivolumab," "BMS-963558," "pembrolizumab," "MK-3475," "atezolizumab," "MPDL3280A," and "phase." Study Selection:Thirty-eight randomized clinical trials evaluating the usage of these ICIs for treatment of advanced solid tumors were identified, resulting in a total of 7551 patients who were eligible for a meta-analysis. Regimens were categorized by class into monotherapy with a PD-1 (programmed cell death protein 1) inhibitor, a CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) inhibitor, or a PD-L1 (programmed cell death 1 ligand 1) inhibitor, and combination therapy with PD-1 plus CTLA-4 inhibitors. Data Extraction and Synthesis:The data were extracted by 1 primary reviewer (R.B.-S.) and then independently reviewed by 2 secondary reviewers (W.T.B. and A.C.G.-C.) following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inferences on the incidence of AEs were made using log-odds random effects models. Main Outcomes and Measures:Incidence of all-grade hypothyroidism, hyperthyroidism, hypophysitis, primary adrenal insufficiency, and insulin-deficient diabetes. Results:Overall, 38 randomized clinical trials comprising 7551 patients were included in this systematic review and meta-analysis. The incidence of both hypothyroidism and hyperthyroidism was highest in patients receiving combination therapy. Patients on the combination regimen were significantly more likely to experience hypothyroidism (odds ratio [OR], 3.81; 95% CI, 2.10-6.91, P?

SUBMITTER: Barroso-Sousa R

PROVIDER: S-EPMC5838579 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis.

Barroso-Sousa Romualdo R Barry William T WT Garrido-Castro Ana C AC Hodi F Stephen FS Min Le L Krop Ian E IE Tolaney Sara M SM

JAMA oncology 20180201 2

<h4>Importance</h4>If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown.<h4>Objective</h4>To compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens.<h4>Data sources</h4>A PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," " ...[more]

PMID: 28973656

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Project description:BACKGROUND:Pneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1 immunotherapy. Most cases of ICI pneumonitis improve or resolve with 4-6 weeks of corticosteroid therapy. Herein, we report the incidence, clinicopathological features and management of patients with non-small cell lung cancer (NSCLC) and melanoma who developed chronic ICI pneumonitis that warrants ?12 weeks of immunosuppression. METHODS:Patients with ICI pneumonitis were identified from institutional databases of ICI-treated patients with advanced melanoma and NSCLC between January 2011 and July 2018. ICI pneumonitis was defined as clinical/radiographic evidence of lung inflammation without alternative diagnoses, adjudicated by a multidisciplinary team. Chronic ICI pneumonitis was defined as pneumonitis that persists or worsens with steroid tapering, and necessitates ?12 weeks of immunosuppression, after ICI discontinuation. Serial chest CT was used to assess radiological features, and tumor response by Response EvaluationCriteria for Solid Tumors V.1.1. Bronchoalveolar lavage fluid (BALF) samples were assessed by cell differential. Lung biopsy samples were evaluated by H&E staining and multiplex immunofluorescence (mIF), where available. RESULTS:Among 299 patients, 44 developed ICI pneumonitis (NSCLC: 5/205; melanoma: 1/94), and of these, 6 experienced chronic ICI pneumonitis. The overall incidence of chronic ICI pneumonitis was thus 2%. Of those who developed chronic ICI pneumonitis: the majority had NSCLC (5/6), all sustained disease control from ICIs, and none had other concurrent irAEs. Timing of chronic ICI pneumonitis development was variable (range: 0-50 months), and occurred at a median of 12 months post ICI start. Recrudescence of ICI pneumonitis occurred at a median of 6 weeks after initial steroid start (range: 3-12 weeks), with all patients requiring steroid reintroduction when tapered to ?10 mg prednisone/equivalent. The median total duration of steroids was 37 weeks (range: 16-43+weeks). Re-emergence of radiographic ICI pneumonitis occurred in the same locations on chest CT, in most cases (5/6). All patients who developed chronic ICI pneumonitis had BALF lymphocytosis on cell differential and organising pneumonia on lung biopsy at initial ICI pneumonitis presentation, with persistent BALF lymphocytosis and brisk CD8+ infiltration on mIF at pneumonitis re-emergence during steroid taper. CONCLUSIONS:A subset of patients who develop pneumonitis from ICIs will develop chronic ICI pneumonitis, that warrants long-term immunosuppression of ?12 weeks, and has distinct clinicopathological features.

Dataset Information

Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis.

Publications

Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis.

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