Adverse Effects of Immune Checkpoint Inhibitors (Programmed Death-1 Inhibitors and Cytotoxic T-Lymphocyte-Associated Protein-4 Inhibitors): Results of a Retrospective Study

Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed death-1 (PD-1)/ligand are increasingly used to treat several types of cancer. These drugs enhance antitumour T-cell activity and therefore induce immune-related adverse effects (irAE), of which gastrointestinal (GI) irAE are among the most frequent and severe. This systematic literature review summarises the clinical manifestations, management and pathophysiology of GI irAE due to immune checkpoint inhibitors. GI irAE induced by anti-CTLA-4 are frequent, potentially severe and resemble IBD, whereas those induced by PD-1 blockade seem to be less frequent and clinically more diverse. Baseline symbiotic gut microbiota is associated with an enhanced antitumour response to immune checkpoint inhibitors and an increased susceptibility to developing enterocolitis, in patients treated with anti-CTLA-4. These findings open new perspectives for possible manipulation of the gut microbiota in order to better identify responders to immune checkpoint inhibitors and to increase their efficacy and safety.

Download Full-text

Immune Checkpoint Inhibitors for Brain Metastases: A Primer for Neurosurgeons

Neurosurgery ◽

10.1093/neuros/nyaa095 ◽

2020 ◽

Vol 87 (3) ◽

pp. E281-E288

Author(s):

Elisa Aquilanti ◽

Priscilla K Brastianos

Keyword(s):

Brain Metastases ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Standard Of Care ◽

Nonsmall Cell Lung Cancer ◽

Immune Recognition ◽

Therapeutic Modalities ◽

Programmed Death 1

Abstract Immune checkpoint inhibitors enhance immune recognition of tumors by interfering with the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed death 1 (PD1) pathways. In the past decade, these agents brought significant improvements to the prognostic outlook of patients with metastatic cancers. Recent data from retrospective analyses and a few prospective studies suggest that checkpoint inhibitors have activity against brain metastases from melanoma and nonsmall cell lung cancer, as single agents or in combination with radiotherapy. Some studies reported intracranial response rates that were comparable with systemic ones. In this review, we provide a comprehensive summary of clinical data supporting the use of anti-CTLA4 and anti-PD1 agents in brain metastases. We also touch upon specific considerations on the assessment of intracranial responses in patients and immunotherapy-specific toxicities. We conclude that a subset of patients with brain metastases benefit from the addition of checkpoint inhibitors to standard of care therapeutic modalities, including radiotherapy and surgery.

Download Full-text

Disparities in the Use of Programmed Death 1 Immune Checkpoint Inhibitors

The Oncologist ◽

10.1634/theoncologist.2017-0673 ◽

2018 ◽

Vol 23 (11) ◽

pp. 1388-1390 ◽

Cited By ~ 3

Author(s):

Jeremy M. O'Connor ◽

Kathi Seidl‐Rathkopf ◽

Aracelis Z. Torres ◽

Paul You ◽

Kenneth R. Carson ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Programmed Death ◽

Programmed Death 1

Download Full-text

Acute kidney injury from immune checkpoint inhibitor use

BMJ Case Reports ◽

10.1136/bcr-2019-231211 ◽

2019 ◽

Vol 12 (10) ◽

pp. e231211 ◽

Cited By ~ 1

Author(s):

Lexis Gordon ◽

Pouneh Dokouhaki ◽

Kimberly Hagel ◽

Bhanu Prasad

Keyword(s):

Acute Kidney Injury ◽

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Kidney Injury ◽

Acute Interstitial Nephritis ◽

Programmed Death ◽

Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

Download Full-text

Immune checkpoint inhibitors in renal cell carcinoma

Clinical Science ◽

10.1042/cs20160894 ◽

2017 ◽

Vol 131 (21) ◽

pp. 2627-2642 ◽

Cited By ~ 25

Author(s):

Kirsty Ross ◽

Rob J. Jones

Keyword(s):

Renal Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Critical Role ◽

Optimal Timing ◽

New Class ◽

Programmed Death ◽

Programmed Death 1 ◽

Immune Manipulation

The immune system has long been known to play a critical role in the body’s defence against cancer, and there have been multiple attempts to harness it for therapeutic gain. Renal cancer was, historically, one of a small number of tumour types where immune manipulation had been shown to be effective. The current generation of immune checkpoint inhibitors are rapidly entering into routine clinical practice in the management of a number of tumour types, including renal cancer, where one drug, nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody (mAb), is licensed for patients who have progressed on prior systemic treatment. Ongoing trials aim to maximize the benefits that can be gained from this new class of drug by exploring optimal timing in the natural course of the disease as well as combinations with other checkpoint inhibitors and drugs from different classes.

Download Full-text

Immunotherapy for Patients with Advanced Urothelial Cancer: Current Evidence and Future Perspectives

BioMed Research International ◽

10.1155/2017/5618174 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 6

Author(s):

Clizia Zichi ◽

Marcello Tucci ◽

Gianmarco Leone ◽

Consuelo Buttigliero ◽

Francesca Vignani ◽

...

Keyword(s):

Bladder Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Adaptive Immune Response ◽

Tumor Infiltrating Lymphocytes ◽

Invasive Disease ◽

Current Evidence ◽

Programmed Death

In recent years, immunotherapy has produced encouraging results in a rapidly increasing number of solid tumors. The responsiveness of bladder cancer to immunotherapy was first established in nonmuscle invasive disease in 1976 with intravesical instillations of bacillus Calmette-Guérin (BCG). Very recently immune checkpoint inhibitors demonstrated good activity and significant efficacy in metastatic disease. In particular the best results were obtained with programmed death-ligand-1 (PD-L1) and programmed death-1 (PD-1) inhibitors, but many other immune checkpoint inhibitors, including anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibodies, are currently under investigation in several trials. Simultaneously other therapeutic strategies which recruit an adaptive immune response against tumoral antigens or employ externally manipulated tumor infiltrating lymphocytes might change the natural history of bladder cancer in the near future. This review describes the rationale for the use of immunotherapy in bladder cancer and discusses recent and ongoing clinical trials with checkpoint inhibitors and other novel immunotherapy agents.

Download Full-text

Predictive biomarkers for programmed death-1/programmed death ligand immune checkpoint inhibitors in nonsmall cell lung cancer

Current Opinion in Oncology ◽

10.1097/cco.0000000000000263 ◽

2016 ◽

Vol 28 (2) ◽

pp. 122-129 ◽

Cited By ~ 27

Author(s):

Jordi Remon ◽

Nathalie Chaput ◽

David Planchard

Keyword(s):

Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Predictive Biomarkers ◽

Nonsmall Cell Lung Cancer ◽

Programmed Death ◽

Programmed Death 1

Download Full-text

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Progresses and Challenges

Frontiers in Oncology ◽

10.3389/fonc.2021.737497 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hao-Tian Liu ◽

Meng-Jie Jiang ◽

Zhu-Jian Deng ◽

Le Li ◽

Jian-Li Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Research Progress ◽

T Cell Signaling ◽

Existing Problems ◽

Programmed Death ◽

New Treatment

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world and its incidence is increasing in many countries. In recent years, with the deepening understanding of the immune and pathological mechanisms of HCC, immunotherapy based on the regulation of tumor immune microenvironment has become a new treatment choice for patients with HCC. Immune checkpoint inhibitors (ICIs) targeting programmed death protein-1, programmed death protein-ligand-1, or cytotoxic T-lymphocyte-associated antigen 4 are the most widely used. Instead of general immune-enhancing therapies, ICIs can reactivate anti-tumor immune responses by disrupting co-inhibitory T cell signaling. In this review, the research progress and existing problems of ICIs in the treatment of HCC in recent years are reviewed.

Download Full-text

PD-L1 SNPs as biomarkers to define benefit in patients with advanced NSCLC treated with immune checkpoint inhibitors

Tumori Journal ◽

10.1177/03008916211014954 ◽

2021 ◽

pp. 030089162110149

Author(s):

Roberta Minari ◽

Francesco Bonatti ◽

Giulia Mazzaschi ◽

Alessandra Dodi ◽

Francesco Facchinetti ◽

...

Keyword(s):

Clinical Outcome ◽

Immune Checkpoint ◽

Clinical Benefit ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Nucleotide Polymorphisms ◽

Entire Cohort ◽

Programmed Death ◽

Programmed Death 1

Objective: To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups. Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association ( p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype ( p = 0.05). Conclusion: PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required.

Download Full-text

Immunotherapy in urothelial cancer: recent data and perspectives

Cancer Urology ◽

10.17650/1726-9776-2017-13-4-16-24 ◽

2018 ◽

Vol 13 (4) ◽

pp. 16-24 ◽

Cited By ~ 2

Author(s):

M. I. Volkova ◽

Ya. V. Gridneva ◽

A. S. Ol’shanskaya

Keyword(s):

Urothelial Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Standard Of Care ◽

Phase Iii ◽

Significant Survival ◽

Programmed Death ◽

Programmed Death 1 ◽

Advanced Urothelial Carcinoma

Immune-checkpoint inhibitors blocking the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) have shown a prominent anti-tumor activity with long-term responses and an acceptable toxicity profile in clinical trials. Pembrolizumab, atezolizumab, nivolumab, avelumab, and durvalumab are anti-PD-1/PD-L1 agents that redefine the standard of care for advanced urothelial carcinoma. CTLA-4 inhibitors are also under investigation in this setting. Phase III trial KEYNOTE-045 has demonstrated significant survival benefit in patients treated with pembrolizumab comparing with the standard second-line chemotherapy. Atezolizumab, nivolumab, avelumab, and durvalumab were also recommended for platinum-pretreated urothelial carcinoma patients based on phase II data. Following investigations of biomarkers such as PD-L1 expression are needed to determine high-responders to immunotherapy. This review article describes the advances in immunotherapy with immune-checkpoint inhibitors.

Download Full-text