Dataset Information

Multidisciplinary Clinical Approach to Cancer Patients with Immune-Related Adverse Events Induced by Checkpoint Inhibitors.

ABSTRACT: Immune-oncology is a major breakthrough in cancer treatment and has become the standard of care for a wide variety of solid organ malignancies. Unfortunately, manipulation of the immune system with checkpoint inhibitors may result in an immune-based attack of normal tissues which can lead to treatment discontinuation. These immune-related adverse events (irAEs) are diverse and affect several organs, constituting a new clinical challenge in the management of cancer patients. The complexity of this scenario requires a multidisciplinary approach that allows the early identification, diagnosis and treatment of specific irAE, ruling out other non-related adverse events. Hospital Clinic has a multidisciplinary team seeking to develop a coordinated strategy to facilitate the access of patients with suspected irAEs to specialised care resulting in harmonised management that guarantees the best patient care. The aim of the manuscript was to describe the current evidence on the management of irAEs reflecting a coordinated multidisciplinary approach to face this clinical challenge regardless of the immunotherapy indication.

SUBMITTER: Londono MC

PROVIDER: S-EPMC7699587 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Multidisciplinary Clinical Approach to Cancer Patients with Immune-Related Adverse Events Induced by Checkpoint Inhibitors.

Londoño Maria-Carlota MC Reig Maria M

Cancers 20201119 11

Immune-oncology is a major breakthrough in cancer treatment and has become the standard of care for a wide variety of solid organ malignancies. Unfortunately, manipulation of the immune system with checkpoint inhibitors may result in an immune-based attack of normal tissues which can lead to treatment discontinuation. These immune-related adverse events (irAEs) are diverse and affect several organs, constituting a new clinical challenge in the management of cancer patients. The complexity of thi ...[more]

PMID: 33228219

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Project description:Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15-60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical biomarker for ICI response in patients is immune-related adverse event (IRAE) onset.IRAEs are thought to represent bystander effects from activated T-cells and it is plausible that patients responding to ICIs would have greater likelihood of autoimmune toxicities (e.g. due to a more competent/treatment-responsive immune system, or cross-reactivity between tumor and host tissue). Earlier studies in melanoma patients however, suggested no association between IRAE onset and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody efficacy. In contrast, a growing body of literature suggests IRAE onset is predictive of anti-programmed cell death protein 1 (PD-1) and anti-PD-L1 antibody response across a variety of solid tumors. Most of these studies report that patients who experienced IRAEs demonstrate marked improvements in progression-free survival, overall survival and overall response rate compared to those lacking toxicity.Key questions regarding the association between IRAE onset and ICI efficacy remain. The most pertinent of these involve whether the association is only relevant for patients treated with anti-PD-1 and anti-PD-L1 antibodies and whether IRAE site, severity, timing of onset and management influence ICI efficacy. Herein, we discuss the seminal studies which have begun to address these questions and have shaped the narrative about the predictive value of IRAE onset for patients on ICIs, in this review.

Project description:BackgroundImmune Checkpoint Inhibitors (ICI) have been progressively used in cancer treatment and produced unique toxicity profiles. This systematic review aims to comprehend the patterns and occurrence of treatment-related adverse events (trAEs) based on ICI.MethodsPICOS/PRISMA methods were used to identify published English-language on PubMed, Web of Science, and Scopus from 2015 to 2020. Published clinical trials on ICI monotherapy, combined ICIs, and ICI plus other treatment with tabulated data on grade≥3 trAEs were included. Odds ratio (OR), χ2 tests were used to analyze for effect size and associations.ResultsThis review included 145 clinical trials involving 21786 patients. Grade 3-5 trAEs were more common with ICI when they were plused with other treatments compared with ICI monotherapy(54.3% versus 17.7%, 46.1%, p<0.05). Grade 3-5 trAEs were also more common with CTLA-4 mAbs compared with anti-PD-1 and anti-PD-L1 (34.2% versus 15.1%, 13.6%, p<0.05). Hyperthyroidism (OR 3.8, 95%CI 1.7-8.6), nausea (OR 3.7, 95%CI 2.5-5.3), diarrhea (OR 2.7, 95%CI 2.2-3.2), colitis (OR 3.4, 95%CI 2.7-4.3), ALT increase (OR 4.9, 95%CI 3.9-6.1), AST increase (OR 3.8, 95%CI 3.0-4.9), pruritus (OR 2.4, 95%CI 1.5-3.9), rash (OR 2.8, 95%CI 2.1-3.8), fatigue (OR 2.8, 95%CI 2.2-3.7), decreased appetite (OR 2.4, 95%CI 1.5-3.8), and hypophysitis (OR 2.0, 95%CI 1.2-3.3) were more frequent with combined ICIs. Diarrhea (OR 8.1, 95%CI 6.4-10.3), colitis (OR 12.2, 95%CI 8.7-17.1), ALT increase (OR 5.1, 95%CI 3.5-7.4), AST increase (OR 4.2, 95%CI 2.8-6.3), pruritus (OR 4.1, 95%CI 2.0-8.4), rash (OR 4.4, 95%CI 2.9-6.8), hypophysitis (OR 12.1, 95%CI 6.3-23.4) were more common with CTLA-4 mAbs; whereas pneumonitis (OR 4.7, 95% CI 2.1-10.3) were more frequent with PD-1 mAbs.ConclusionsDifferent immune checkpoint inhibitors are associated with different treatment-related adverse events profiles. A comprehensive data in this systematic review will provide comprehensive information for clinicians.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) has emerged as a popular cancer treatment approach. However, non-specific activation of T cells by ICIs can lead to immune-related adverse events (irAEs), including specific rheumatic manifestations. The study aimed to explore the current trend of ICIs associated rheumatic irAEs and summarize the knowledge structure through bibliometric methods.MethodsThe Web of Science Core Collection database (WoSCC) was selected for retrieving literature on ICIs associated rheumatic irAEs. To evaluate contributions from different countries/regions, institutions, journals, and authors, bibliometric analysis software, including VOSviewer and CiteSpace, as well as bibliometric online platforms, were utilized to construct and visualize bibliometric networks. Through the systematic review of this knowledge domain, future research directions were determined.ResultsIn This study, a total of 803 publications on ICIs-associated rheumatic irAEs were included for analysis. The distribution of these publications revealed two distinct growth phases: a stable phase between 2007 to 2015 followed by rapid growth from 2016 to 2020. The United States emerged as the top contributor in terms of publications, citations, and h-index, with the majority of leading institutions and funding agencies located there. Apart from government funding, pharmaceutical companies such as Bristol Myers Squibb and Merck Company also play a significant role in drug development and research. Analysis of keywords and citation bursts indicated that the initial burst was related to "monoclonal antibody," "anti-CLTA4 antibody," and "melanoma". This was followed by a rise in interest related to "sarcoidosis," "safety," "inflammatory arthritis," and "preexisting autoimmune."ConclusionThis study summarized the global research trends concerning ICIs associated rheumatic irAEs. The findings can provide valuable insights into the current understanding of rheumatic irAEs, highlight the research trend and developments in the field. Future efforts should focus on developing classification criteria and guidelines, conducting prospective studies, investigating the mechanisms involved, and identifying biomarkers for prediction and monitoring of these events.

Dataset Information

Multidisciplinary Clinical Approach to Cancer Patients with Immune-Related Adverse Events Induced by Checkpoint Inhibitors.

Publications

Multidisciplinary Clinical Approach to Cancer Patients with Immune-Related Adverse Events Induced by Checkpoint Inhibitors.

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