scholarly journals Immune Checkpoint Inhibition in Advanced Bladder and Kidney Cancer: Responses and Further Management

2021 ◽  
pp. e182-e189
Author(s):  
Mamta Parikh ◽  
Thomas Powles
Keyword(s):  
Bladder Cancer ◽  
Kidney Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Treatment Regimens ◽  
Metastatic Bladder Cancer ◽  
Platinum Based Chemotherapy

Immune checkpoint inhibitors have an established role in the treatment of newly diagnosed metastatic kidney cancer. Treatment regimens combining nivolumab plus ipilimumab, pembrolizumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib have demonstrated superior overall survival compared with sunitinib in randomized studies. Response rates vary from 42% to 71.1% with these combinations. Atezolizumab and pembrolizumab have been approved for the treatment of cisplatin-ineligible patients with metastatic bladder cancer. These and other checkpoint inhibitors have been studied in metastatic bladder cancer and are routinely used after progression on platinum-based chemotherapy. Durable responses are observed in bladder and kidney cancer. Although some patients may experience immune-related adverse events requiring treatment discontinuation, a portion of these patients will continue to experience a response off-therapy. At the time of progression, patients with metastatic kidney cancer may be treated with antiangiogenesis agents, and there are data suggesting that they may also be treated with a rechallenge of immunotherapy. In patients with metastatic bladder cancer who have progression after immune checkpoint inhibition, there are considerable data supporting the use of enfortumab vedotin. Ongoing studies are evaluating novel combinations of immune checkpoint inhibitors with other agents; thus, the treatment landscape of metastatic bladder and kidney cancer is expected to continue to evolve rapidly.

scholarly journals Immune Checkpoint Inhibition and the Prevalence of Autoimmune Disorders Among Patients With Lung and Renal Cancer

2017 ◽  
Vol 16 ◽  
pp. 117693511771252 ◽  
Author(s):  
Sherif M El-Refai ◽  
Joshua D Brown ◽  
Esther P Black ◽  
Jeffery C Talbert
Keyword(s):  
Autoimmune Diseases ◽  
Renal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
International Classification Of Diseases ◽  
Autoimmune Disorders ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Autoimmune Condition

Purpose: Immune checkpoint inhibition reactivates the immune response against cancer cells in multiple tissue types and has been shown to induce durable responses. However, for patients with autoimmune disorders, their conditions can worsen with this reactivation. We sought to identify, among patients with lung and renal cancer, how many harbor a comorbid autoimmune condition and may be at risk of worsening their condition while on immune checkpoint inhibitors such as nivolumab and pembrolizumab. Methods: An administrative health care claims database, Truven MarketScan, was used to identify patients diagnosed with lung and renal cancer from 2010 to 2013. We assessed patients for diagnosis of autoimmune diseases 1 year prior to or after diagnosis of cancer using International Classification of Diseases, Ninth Revision codes for 41 autoimmune diseases. Baseline characteristics and other comorbid conditions were recorded. Results: More than 25% of patients with both lung and renal cancer had a comorbid autoimmune condition between 2010 and 2013 and were more likely to be women, older, and have more baseline comorbidities. Conclusions: This population presents a dilemma to physicians when deciding to treat with immune checkpoint inhibitors and risk immune-related adverse events. Future evaluation of real-world use of immune checkpoint inhibitors in patients with cancer with autoimmune diseases will be needed.

Immune-related intestinal pseudo-obstruction associated with nivolumab treatment in a lung cancer patient

2017 ◽  
Vol 25 (2) ◽  
pp. 487-491 ◽  
Author(s):  
Georgios Fragulidis ◽  
Eirini Pantiora ◽  
Vasiliki Michalaki ◽  
Elissaios Kontis ◽  
Elias Primetis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
High Dose ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Gradual Improvement ◽  
Organ Systems

Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a new therapeutic approach with significant survival benefit for patients with several cancer types. However, their use can be associated with unique immune-related adverse effects as a consequence of impaired self-tolerance due to loss of T-cell inhibition via a nonselective activation of the immune system. Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy with remarkable responses in nonsmall cell lung cancer patients. We present a 62-year-old Caucasian male with recurrent lung adenocarcinoma and currently under third-line therapy with nivolumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After four days of conservative treatment, the patient underwent exploratory laparotomy where no cause of ileus was discovered. Postoperative the ileus persisted and considering that an adverse effect of the immune checkpoint inhibition therapy occurred, the patient received high-dose prednisone resulting in gradual improvement of symptoms. Immune checkpoint inhibitors may induce adverse effects to unaffected organ systems and tissues including the skin, gastrointestinal, hepatic, pulmonary, and endocrine system. The mainstay treatment consists of immunosuppression with corticosteroids in the majority of cases. As the clinical use of immune checkpoint inhibitors is expanding rapidly, there is an emergence of unique immune-related adverse effects in a growing patient population. Gaining early awareness is essential in these patients in order to ensure prompt diagnosis and management.

scholarly journals Immune checkpoint inhibitors for metastatic bladder cancer

2017 ◽  
Vol 6 (S4) ◽  
pp. S720-S732
Author(s):  
Marta Cubelli ◽  
Vincenzo Di Nunno ◽  
Karim Rihawi ◽  
Francesco Massari
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Metastatic Bladder Cancer

Circulating cellular biomarkers associated with delayed time to progression among bladder cancer patients treated with immune checkpoint inhibitors.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 398-398
Author(s):  
Vadim S Koshkin ◽  
Terence W. Friedlander ◽  
Patricia Li ◽  
Joseph Schonhoft ◽  
Rachel Krupa ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Significant Trend ◽  
Response To Treatment ◽  
Time To Progression ◽  
Metastatic Bladder Cancer ◽  
Delayed Time

398 Background: Circulating tumor cells (CTCs) are an important emerging biomarker in bladder cancer that allow for a minimally invasive assessment of tumor activity and response to treatment. Characterization of CTC and other single cell populations associated with improved clinical outcomes can help guide treatment recommendations for patients with metastatic bladder cancer. Methods: Patients with metastatic bladder cancer who received treatment with anti-PD-1 or anti-PD-L1 agents were enrolled in this study. Patient response to treatment was assessed by treating physicians according to RECIST v1.1. Blood samples were prospectively collected from patients prior to the initiation of therapy and then while on treatment and shipped to Epic Sciences for processing. All nucleated cells were subjected to immunofluorescent (IF) staining and CTC and leukocyte identification by fluorescent scanners using algorithmic analysis. Kaplan-Meier analysis was utilized to compare time to progression of patients whose CTC and leukocyte values were above and below several pre-determined parameters. Results: A total of 27 patients (median age 74 years, 70% male) were enrolled in this study and were treated with anti-PD-1/PD-L1 agents pembrolizumab (n=15), atezolizumab (n=11), or nivolumab (n=1). For 20 patients who had evaluable responses, objective response rate (ORR) was 2/20 (10%), all partial responses; another 5/20 (35%) had stable disease. Increased CD4% (>8% of total leukocytes) was associated with delayed time to progression (TTP) (p=0.002) whereas increased baseline total CTCs (>2) had a statistically non-significant trend towards shorter TTP (p=0.09). Baseline CD8%, CD4/CD8 ratio and CTC PD-L1 status were not associated with TTP. Conclusions: In a preliminary analysis among metastatic bladder cancer patients treated with immune checkpoint inhibitors, patients with an increased baseline CTC count had a statistically non-significant trend towards shorter TTP whereas increased baseline CD4 cells had an association with delayed TTP. This prospective study is ongoing, and the results will be further validated in larger patient cohorts.

scholarly journals Focus on Biochemical and Clinical Predictors of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma: Where Do We Stand?

2020 ◽  
Vol 21 (21) ◽  
pp. 7935 ◽  
Author(s):  
Giandomenico Roviello ◽  
Martina Catalano ◽  
Stefania Nobili ◽  
Raffaella Santi ◽  
Enrico Mini ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
The United States ◽  
Variable Response ◽  
Clinical Predictors ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

Urothelial bladder cancer is one of the most lethal cancers worldwide with barely 5% five-year survival in patients with metastatic disease. Intravesical immunotherapy with Bacillus Calmette-Guérin and platinum-based chemotherapy are currently the standard of care for non-muscle invasive and advanced or metastatic urothelial cancer (mUC), respectively. Recently, a subset of patients with locally advanced or mUC has shown to be responsive to immune checkpoint inhibitors (ICIs), e.g., the anti-cytotoxic T-lymphocyte-associated protein 4 and programmed cell death -1/programmed death-ligand1 (PD-1/PD-L1) antibodies. Due to the relevant clinical benefit of immunotherapy for mUC, in 2016, the United States Food and Drug Administration (FDA) approved five immunotherapeutic agents as second-line or first-line treatments for patients with advanced bladder cancer who did not profit from or were ineligible for standard therapy. In this review, we discuss the role of immunotherapy in bladder cancer and recent clinical applications of PD-1/PD-L1 blockade in mUC. Furthermore, we evaluate a variable response rate to ICIs treatment and outline potential biomarkers predictive of immunotherapy response.

scholarly journals Immune checkpoint inhibitors for metastatic bladder cancer

2018 ◽  
Vol 64 ◽  
pp. 11-20 ◽  
Author(s):  
Francesco Massari ◽  
Vincenzo Di Nunno ◽  
Marta Cubelli ◽  
Matteo Santoni ◽  
Michelangelo Fiorentino ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Metastatic Bladder Cancer

scholarly journals Neurosarcoidosis following Immune Checkpoint Inhibition

2018 ◽  
Vol 11 (2) ◽  
pp. 521-526 ◽  
Author(s):  
Anastasie M. Dunn-Pirio ◽  
Suma Shah ◽  
Christopher Eckstein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Relevant Literature ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Cns Involvement ◽  
Cns Metastases

Recently, immune checkpoint inhibitors have revolutionized cancer care by enhancing anti-tumor immunity. However, by virtue of stimulating the immune system, they can lead to immune-related adverse events (irAEs). Neurologic irAEs are uncommon but are becoming increasingly recognized and can be quite serious or even fatal. Furthermore, central nervous system (CNS) manifestations may be difficult to distinguish from CNS metastases, posing management challenges. Here, we describe a patient who developed exacerbation of sarcoidosis leading to CNS involvement following dual checkpoint blockade with nivolumab and ipilimumab for metastatic melanoma and review the relevant literature.

scholarly journals Challenges to Successful Implementation of the Immune Checkpoint Inhibitors for Treatment of Glioblastoma

2020 ◽  
Vol 21 (8) ◽  
pp. 2759 ◽  
Author(s):  
Stephanie Sanders ◽  
Waldemar Debinski
Keyword(s):  
Malignant Glioma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Successful Implementation ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition

Glioblastoma (GBM) is the most common and aggressive malignant glioma, treatment of which has not improved significantly in many years. This is due to the unique challenges that GBM tumors present when designing and implementing therapies. Recently, immunotherapy in the form of immune checkpoint inhibition (ICI) has revolutionized the treatment of various malignancies. The application of immune checkpoint inhibition in GBM treatment has shown promising preclinical results. Unfortunately, this has met with little to no success in the clinic thus far. In this review, we will discuss the challenges presented by GBM tumors that likely limit the effect of ICI and discuss the approaches being tested to overcome these challenges.

Sign in / Sign up

Export Citation Format

Share Document