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Diagnosis and Management of Hematological Adverse Events Induced by Immune Checkpoint Inhibitors: A Systematic Review.

ABSTRACT: There has been less volume of literature focusing on the Immune-related Hematological Adverse Drug Events (Hem-irAEs) of Immune Checkpoint Inhibitors (ICPis) in cancer patients. Furthermore, there has been no consensus about the management of hematological toxicity from immunotherapy in the recently published practice guidelines by the European Society for Medical Oncology (ESMO). We conducted a systematic review of case reports/series to describe the diagnosis and management of potentially rare and unrecognized Hem-irAEs. We searched Medline, OVID, Web of Science for eligible articles. Data were extracted on patient characteristics, Hem-irAEs, and management strategies. We performed quality assessment using the Pierson-5 evaluation scheme and causality assessment using the Naranjo scale. Our search retrieved 49 articles that described 118 cases. The majority of patients had melanoma (57.6%) and lung cancer (26.3%). The most common Hem-irAEs reported with ICPis (such as nivolumab, ipilimumab, and pembrolizumab) were thrombocytopenia, hemolytic and aplastic anemias. Less reported adverse events included agranulocytosis and neutropenia. Steroids were commonly used to treat these adverse events with frequent success. Other used strategies included intravenous immunoglobulins (IVIG), rituximab, and transfusion of blood components. The findings of this review provide more insights into the diagnosis and management of the rarely reported Hem-irAEs of ICPis.

SUBMITTER: Omar NE

PROVIDER: S-EPMC7640759 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Diagnosis and Management of Hematological Adverse Events Induced by Immune Checkpoint Inhibitors: A Systematic Review.

Omar Nabil E NE El-Fass Kareem A KA Abushouk Abdelrahman I AI Elbaghdady Noha N Barakat Abd Elmonem M AEM Noreldin Ahmed E AE Johar Dina D Yassin Mohamed M Hamad Anas A Elazzazy Shereen S Dermime Said S

Frontiers in immunology 20201021

There has been less volume of literature focusing on the Immune-related Hematological Adverse Drug Events (Hem-irAEs) of Immune Checkpoint Inhibitors (ICPis) in cancer patients. Furthermore, there has been no consensus about the management of hematological toxicity from immunotherapy in the recently published practice guidelines by the European Society for Medical Oncology (ESMO). We conducted a systematic review of case reports/series to describe the diagnosis and management of potentially rare ...[more]

PMID: 33193289

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Project description:Unlabelled: In recent years, immune checkpoint inhibitors have emerged as effective therapies for advanced neoplasias. As new checkpoint target blockers become available and additional tumor locations tested, their use is expected to increase within a short time. Immune-related adverse events (irAEs) affecting the endocrine system are among the most frequent and complex toxicities. Some may be life-threatening if not recognized; hence, appropriate guidance for oncologists is needed. Despite their high incidence, endocrine irAEs have not been fully described for all immunotherapy agents available. This article is a narrative review of endocrinopathies associated with cytotoxic T lymphocyte-associated antigen-4, blockade of programmed death receptor 1 and its ligand inhibitors, and their combination. Thyroid dysfunction is the most frequent irAE reported, and hypophysitis is characteristic of ipilimumab. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for clinical management are suggested. Heterogeneous terminology and lack of appropriate resolution criteria in clinical trials make adequate evaluation of endocrine AEs difficult. It is necessary to standardize definitions to contrast incidences and characterize toxicity patterns. To provide optimal care, a multidisciplinary team that includes endocrinology specialists is recommended.Implications for practiceImmune checkpoint inhibitors are already part of oncologists' therapeutic arsenal as effective therapies for otherwise untreatable neoplasias, such as metastatic melanoma or lung cancer. Their use is expected to increase exponentially in the near future as additional agents become available and their approval is extended to different tumor types. Adverse events affecting the endocrine system are among the most frequent and complex toxicities oncologists may face, and some may be life-threatening if not recognized. This study reviews endocrinopathies associated to immune checkpoint inhibitors available to date. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for management are proposed.

Project description:Background: Immune checkpoint blockade has revolutionized the treatment of multiple malignancies. Currently, however, the effect is not universal, with objective response rates (ORR) of about 15-25%, and even lower for some cancers. Abnormal vasculature is a hallmark of most solid tumors and plays a role in immune evasion. Growing body of evidence suggests that vascular normalization and immune reprogramming could operate synergistic effect, resulting in an enhanced therapeutic efficacy. However, the benefit of antitumor efficacy must be weighed against the risk of added toxicity. In this systematic review, we summarize severe toxicity observed in such a kind of combination regimen. Methods: PubMed and Embase were searched for English references published up to May 31, 2019, with MeSH and keywords search terms of immune checkpoint inhibitors (ICIs) and antiangiogenic agents approved for using in solid tumors. Studies performing concomitant use of ICIs and antiangiogenic agents, and also reporting severe treatment-related adverse events (trAEs) (?grade 3), were included for further analysis. Results: A total of 32 studies including a total of 2,324 participants were analyzed. Limited available data suggests that both antiangiogenic monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) show potential risk of increasing treatment-related toxicity when combined with ICIs. Overall, the total incidence of severe adverse events (AEs) associated with ICIs plus mAbs (44.5%) is lower than that of ICIs plus TKIs (60.1%). However, the trAEs observed in combination therapy are mostly consistent with the known safety profiles of corresponding monotherapy, and they seem to be largely related to antiangiogenic agents, rather than a true immune-related adverse event (irAE) predominantly due to ICIs. The majority of trAEs are intervened by holding ICI treatment and adding corticosteroids, as well as reducing dose or adjusting administration frequency of the antiangiogenic drugs. Conclusions: Concurrent use of ICIs and antiangiogenic agents shows potential treatment-related toxicity. Further research is required to compare the efficacy and safety of the combination regimen and corresponding monotherapy and identify predictive biomarkers, as well as explore dose, duration, and sequencing schedules of drugs.

Project description:Background: The musculoskeletal toxicity of immune checkpoint inhibitors (ICIs) is receiving increasing attention with clinical experience. Nevertheless, the absence of a systematic investigation into the musculoskeletal toxicity profile of ICIs currently results in the under-recognition of associated adverse events. Further and more comprehensive investigations are warranted to delineate the musculoskeletal toxicity profile of ICIs and characterize these adverse events. Material and methods: The present study employed the FDA Adverse Event Reporting System database to collect adverse events between January 2010 and March 2021. We utilized both the reporting odds ratio and the Bayesian confidence propagation neural network algorithms to identify suspected musculoskeletal adverse events induced by ICIs. Subsequently, the clinical characteristics and comorbidities of the major musculoskeletal adverse events were analyzed. The risk of causing these events with combination therapy versus monotherapy was compared using logistic regression model and Ω shrinkage measure model. Results: The musculoskeletal toxicity induced by ICIs primarily involves muscle tissue, including neuromuscular junctions, fascia, tendons, and tendon sheaths, as well as joints, spine, and bones, including cartilage. The toxicity profile of PD-1/PD-L1 and CTLA-4 inhibitors varies, wherein the PD-1 inhibitor pembrolizumab exhibits a heightened overall risk of inducing musculoskeletal adverse events. The major ICIs-induce musculoskeletal adverse events, encompassing conditions such as myositis, neuromyopathy (including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Guillain-Barré syndrome, and Chronic inflammatory demyelinating polyradiculoneuropathy), arthritis, fractures, myelitis, spinal stenosis, Sjogren's syndrome, fasciitis, tenosynovitis, rhabdomyolysis, rheumatoid myalgia, and chondrocalcinosis. Our study provides clinical characteristics and comorbidities of the major ICIs-induced musculoskeletal adverse events. Furthermore, the combination therapy of nivolumab and ipilimumab does not result in a statistically significant escalation of the risk associated with the major musculoskeletal adverse events. Conclusion: Immune checkpoint inhibitors administration triggers a range of musculoskeletal adverse events, warranting the optimization of their management during clinical practice.

Dataset Information

Diagnosis and Management of Hematological Adverse Events Induced by Immune Checkpoint Inhibitors: A Systematic Review.

Publications

Diagnosis and Management of Hematological Adverse Events Induced by Immune Checkpoint Inhibitors: A Systematic Review.

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