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Endocrinopathies Associated with Immune Checkpoint Inhibitor Cancer Treatment: A Review.

ABSTRACT: Treatment with immune checkpoint inhibitors has shown efficacy against a variety of cancer types. The effects of nivolumab and pembrolizumab on lung cancer have been reported, and further therapeutic advances are ongoing. The side effects of immune checkpoint inhibitors are very different from those of conventional cytocidal anticancer drugs and molecular targeted drugs, and they involve various organs such as the digestive and respiratory organs, thyroid and pituitary glands, and skin. The generic term for such adverse events is immune-related adverse events (irAEs). They are relatively infrequent, and, if mild, treatment with immune checkpoint inhibitors can be continued with careful control. However, early detection and appropriate treatment are critical, as moderate-to-severe irAEs are associated with markedly reduced organ function and quality of life, with fatal consequences in some cases. Of these, endocrinopathies caused by immune checkpoint inhibitors are sometimes difficult to distinguish from nonspecific symptoms in patients with advanced cancer and may have serious outcomes when the diagnosis is delayed. Therefore, it is necessary to anticipate and appropriately address the onset of endocrinopathies during treatment with immune checkpoint inhibitors. Here, we present a review of endocrine disorders caused by immune checkpoint inhibitor treatment.

SUBMITTER: Okura N

PROVIDER: S-EPMC7409155 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Endocrinopathies Associated with Immune Checkpoint Inhibitor Cancer Treatment: A Review.

Okura Naoko N Asano Mai M Uchino Junji J Morimoto Yoshie Y Iwasaku Masahiro M Kaneko Yoshiko Y Yamada Tadaaki T Fukui Michiaki M Takayama Koichi K

Journal of clinical medicine 20200629 7

Treatment with immune checkpoint inhibitors has shown efficacy against a variety of cancer types. The effects of nivolumab and pembrolizumab on lung cancer have been reported, and further therapeutic advances are ongoing. The side effects of immune checkpoint inhibitors are very different from those of conventional cytocidal anticancer drugs and molecular targeted drugs, and they involve various organs such as the digestive and respiratory organs, thyroid and pituitary glands, and skin. The gene ...[more]

PMID: 32610470

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Project description:Background:Since 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug's AEs (which may change during a drug's life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O'Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed. Methods:In July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles' references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized. Results:One hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing's syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5?months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis. Conclusions:The spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.

Project description:Introduction Immune checkpoint inhibitors (ICIs) are increasingly used to treat cancers. Kidney immune-related adverse events (IRAEs) are now well recognized, with the incidence of IRAEs ranging from 2% to 5%. Most of the initial data related to kidney IRAEs have focused on acute interstitial nephritis (AIN). There are minimal data on the types and relative frequencies of glomerular diseases associated with ICIs, their treatment, and outcomes. Methods We performed a systematic review and meta-analysis of all biopsy-proven published cases/series of glomerular pathology associated with ICIs. We searched the MEDLINE, EMBASE, and Cochrane databases from inception to February 2020. We abstracted patient-level data, including demographics, cancer and ICI therapy details, and characteristics of kidney injury. Results After screening, 27 articles with 45 cases of biopsy-confirmed ICI-associated glomerular disease were identified. Several lesion types were observed, with the most frequent being pauci-immune glomerulonephritis (GN) and renal vasculitis (27%), podocytopathies (24%), and complement 3 GN (C3GN; 11%). Concomitant AIN was reported in 41%. Most patients had ICIs discontinued (88%), and nearly all received corticosteroid treatment (98%). Renal replacement therapy (RRT) was required in 25%. Most patients had full (31%) or partial (42%) recovery from acute kidney injury (AKI), although 19% remained dialysis-dependent, and approximately one-third died. Complete or partial remission of proteinuria was achieved in 45% and 38%, respectively. Conclusion Multiple forms of ICI-associated glomerular disease have been described. Pauci-immune GN, podocytopathies, and C3GN are the most frequently reported lesions. ICI-associated glomerular disease may be associated with poor kidney and mortality outcomes. Oncologists and nephrologists must be aware of glomerular pathologies associated with ICIs and consider obtaining a kidney biopsy specimen when features atypical for AIN are present. Graphical abstract

Project description:ObjectivesBased on the acknowledged organ-specific immune microenvironment, little is known regarding the efficacy of immunotherapy in patients with lung cancer according to metastatic sites. This meta-analysis aimed to explore the efficacy of immune checkpoint inhibitors (ICIs) vs chemotherapy in patients with lung cancer with liver metastases (LM) or brain metastases (BM).DesignMeta-analysis and systematic review.Data sourcesWe systematically searched in electronic databases (PubMed, EMBASE, Cochrane Library and Web of Science), up to 31 January 2022. We also reviewed the abstracts from major international conferences. Eligibility criteria were randomised controlled phase II or III trials reporting the overall survival (OS) or progression-free survival (PFS) of LM or BM subsets.Data extraction and synthesisHazard ratios (HRs) with 95% CIs for OS and PFS were extracted and aggregated using a random-effects model.ResultsTwenty-four randomised controlled trials with available outcomes for patients with BMs or LMs were identified. A total of 1124 patients with BM and 2077 patients with LM were included in the analysis. The pooled OS HR of patients with LMs was 0.83 (95% CI 0.72 to 0.95), and that of patients without LM 0.73 (95% CI 0.69 to 0.79). LM was associated with less benefits from ICIs. In patients with BM treated with ICIs, the pooled OS HR compared with the control arms was 0.71 (95% CI 0.53 to 0.94). Subgroup analyses by histology suggested that only patients with non-small cell lung cancer (NSCLC) with BM could gain benefit from ICIs (HR 0.53, 95% CI 0.41 to 0.68). BM negatively influenced efficacy of immunotherapy in patients with small cell lung cancer.ConclusionsOur results showed immunotherapy demonstrated efficacy in patients with lung cancer with LM and BM, survival benefits dominantly favoured patients with NSCLC. Patients with lung cancer with LM obtained less benefits from ICIs than those without. Therefore, organ-specific immunotherapeutic approaches should be considered.Prospero registration numberCRD42020212797.

Project description:Objective To investigate the clinical features of active tuberculosis (TB) infection due to immune checkpoint inhibitors (ICIs) treatment in patients with advanced cancer. Methods We report the diagnosis and treatment of a case of pulmonary malignancy (squamous cell carcinoma, cT4N3M0 IIIC), secondary to active TB infection following ICIs therapy. Moreover, we summarize and analyze other related cases collected from the China National Knowledge Infrastructure (CNKI), Wanfang Database, PubMed, the Web of Science, and EMBASE (up to October 2021). Results A total of 23 patients, including 20 males and 3 females who were aged 49-87 years with a median age of 65 years, were included in the study. Twenty-two patients were diagnosed by Mycobacterium tuberculosis culture or DNA polymerase chain reaction (PCR), while the remaining patient was diagnosed by tuberculin purified protein derivative and pleural biopsy. One case had an interferon-gamma release assay (IGRA) to rule out latent TB infection prior to the application of ICI. Fifteen patients received an anti-tuberculosis regimen. Among the 20 patients with a description of clinical regression, 13 improved and 7 died. Seven of the patients who improved were treated with ICI again and four of them did not experience a recurrence or worsening of TB. The case diagnosed in our hospital also improved after receiving anti-TB treatment after stopping ICI therapy, and continued chemotherapy on the basis of anti-TB treatment, and his condition is relatively stable at present. Conclusion Due to the lack of specificity of TB infection following ICIs therapy, patients should be followed for fever and respiratory symptoms for 6.3 months after drug administration. It is recommended that IGRA should be performed before ICIs therapy and the development of TB during immunotherapy in patients who are positive in IGRA should be closely monitored. The symptoms of TB in most patients can be improved with ICIs withdrawal and anti-TB treatment, but there is still a need to be alert to the potentially fatal risk of TB.

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Endocrinopathies Associated with Immune Checkpoint Inhibitor Cancer Treatment: A Review.

Publications

Endocrinopathies Associated with Immune Checkpoint Inhibitor Cancer Treatment: A Review.

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