scholarly journals Immunotherapy toxicity: identification and management

Author(s):  
O. Gumusay ◽  
J. Callan ◽  
H. S. Rugo

AbstractThe widespread adoption of immunotherapy has revolutionized the treatment of various cancer types, including metastatic triple-negative breast cancer (TNBC), which has long been associated with poor prognostic outcomes. In particular, immune checkpoint inhibitors (ICIs) that target and inhibit programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have shown promising results in the treatment of patients with metastatic TNBC. However, while manipulating the immune system to induce antitumor response, ICIs can also lead to a unique set of immune-related adverse events (IRAEs), which differ from standard chemotherapy toxicities due to their immune-based origin. These toxicities require highly specific management, including guidance from multidisciplinary specialists. The primary treatment strategy against IRAEs is systemic corticosteroid use, but additional treatment approaches may also involve supportive care, additional immunosuppression, and concurrent treatment delay or discontinuation. Given the rising prevalence of ICI therapy, it is essential to educate clinicians on the presentation and management of these potentially life-threatening events so that they are identified early and treated appropriately. Using data from recent clinical trials, this review will focus on known IRAEs, particularly those seen in patients with breast cancer, and will summarize their prevalence, severity, and outcomes. We will discuss optimal strategies for early recognition and management, as well as approaches toward cautious retreatment following resolution of IRAEs.

Author(s):  
Daniele Balducci ◽  
Claudia Quatraccioni ◽  
Antonio Benedetti ◽  
Marco Marzioni ◽  
Luca Maroni

Immune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel drugs in the anti-cancer therapy. Their use in different types of advanced cancer has shown good results and an increase in survival rates. However, immune-related adverse events (irAEs) are frequent and often require special care. IrAEs may affect all the organs, but they are most commonly seen in skin, lungs, endocrine glands and in the gastrointestinal tract where small bowel, colon, the liver and/or the pancreas can be involved. Despite being usually mild and self-resolving, irAEs may present in severe and life-threatening forms, causing the withdrawal of anti-cancer therapy. IrAEs, therefore, represent a challenging condition to manage that often requires the cooperation between the oncologists and the gastroenterologists in order to identify and treat them adequately.


2020 ◽  
pp. 33-38
Author(s):  
I. A. Hromakova ◽  
P. P. Sorochan ◽  
N. E. Prokhach ◽  
I. N. Ponamarov ◽  
I. S. Hromakova ◽  
...  

Despite advances in early detection and treatment, breast cancer remains the deadliest oncopathology for women worldwide. Today there is an urgent need for new approaches to this disease treatment. Recently, immune therapy, especially inhibitors of immune checkpoints, has taken the lead when fighting against cancer. Blocking immune checkpoints is an effective approach to enhance the effector T cell function. Immune checkpoint blockers, namely inhibitors of cytotoxic T−lymphocyte−associated antigen 4 (CTLA−4), programmed cell death protein 1 (PD−1) and ligand 1 of programmed cell death protein 1 (PD−L1) are approved by the US Food and Drug Association (FDA) to be used in various solid tumors, refractory cancers with microsatellite instability, classical Hodgkin's lymphoma. In March 2019, the first inhibitor for the treatment of breast cancer was approved, i.e. atezolizumab (anti−PD−L1) in combination with nab−paclitaxel in the patients with metastatic triple−negative breast cancer, which aroused the interest of experts in the study of immunotherapeutic agents for the treatment of these patients. The review presents the results of using the inhibitors of immune control points in monotherapy and in combination with standard methods of antitumor treatment (chemotherapy and radiotherapy, targeted therapy) in patients with breast cancer. Information on potential biomarkers of response to immunotherapy in breast cancer is presented. Key words: breast cancer, checkpoint inhibitors, biomarkers of response.


2020 ◽  
Vol 21 (19) ◽  
pp. 7195 ◽  
Author(s):  
Grzegorz Sławiński ◽  
Anna Wrona ◽  
Alicja Dąbrowska-Kugacka ◽  
Grzegorz Raczak ◽  
Ewa Lewicka

Lung cancer is a major cause of cancer-related mortality worldwide, both in men and women. The vast majority of patients are diagnosed with non-small-cell lung cancer (NSCLC, 80–85% of lung cancer cases). Therapeutics named immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in the last decade. They are monoclonal antibodies, and those directed against PD-1 (programmed cell death protein 1) or PD-L1 (programmed cell death-ligand 1) have been used in the treatment of lung cancer and significantly improved the prognosis of NSCLC patients. However, during treatment with ICIs, immune-related adverse events (irAEs) can occur in any organ and any tissue. At the same time, although cardiac irAEs are relatively rare compared to irAEs in other organs, they have a high mortality rate. The two most common clinical manifestations of immunotherapy-related cardiotoxicity are myocarditis and pericarditis. Various types of arrhythmias have been reported in patients treated with ICIs, including the occurrence of life-threatening complete atrioventricular block or ventricular tachyarrhythmias. Here, we aim to summarize the incidence, clinical manifestations, underlying mechanisms, diagnosis, and treatment strategies for ICI-associated cardiotoxicity as these issues become very important in view of the increasing use of ICI in the treatment of lung cancer.


2021 ◽  
Vol 12 ◽  
Author(s):  
Dongfeng Feng ◽  
Yaping Guan ◽  
Mingguo Liu ◽  
Shuqian He ◽  
Weipeng Zhao ◽  
...  

Immunotherapy with immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors, has revolutionized the systematic treatment of advanced and metastatic solid tumors. However, the response rate to ICIs is unsatisfactory, and unexpected hyperprogressive disease (HPD) is even observed in a small subgroup of patients. Patients with HPD usually have worsening clinical symptoms and poorer survival, and therapeutic strategies are extremely limited. Here, we presented a patient with HPD who had used a PD-L1 inhibitor and was highly responsive to the sequential use of a PD-1 inhibitor. A 67-year-old woman with metastatic triple-negative breast cancer was treated with pembrolizumab plus chemotherapy after progression on previous multiple-line chemotherapy treatments. After 2 cycles of treatments, she rapidly developed HPD, as confirmed by radiological evaluation and worsening symptoms. At that time, pembrolizumab was discontinued, and she switched to the PD-L1 inhibitor atezolizumab plus chemotherapy. This patient partially responded to atezolizumab plus chemotherapy without experiencing severe drug-related adverse effects. This is the first reported case of metastatic breast cancer in a patient with radiologically confirmed HPD after pembrolizumab therapy in which successful rechallenge with atezolizumab relieved clinical symptoms. Further studies with larger sample sizes involving a deeper translational investigation of HPD are needed to confirm the efficacy and mechanism of sequential application of different ICIs for the clinical management of HPD.


2020 ◽  
Vol 51 (1) ◽  
pp. 20-27
Author(s):  
Akihito Kawazoe ◽  
Kohei Shitara ◽  
Narikazu Boku ◽  
Takaki Yoshikawa ◽  
Masanori Terashima

Abstract Recently, immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) monoclonal antibodies have improved the overall survival of various types of cancers including advanced gastric cancer (AGC). Until now, two ant-PD-1 inhibitors were approved for AGC in Japan: nivolumab as third- or later-line treatment for AGC and pembrolizumab for previously treated patients with microsatellite instability-high tumours. However, a limited number of patients achieved clinical benefit, highlighting the importance of the better selection of patients or additional treatment to overcome resistance to PD-1/PD-L1 blockade. This review focused on pivotal clinical trials, biomarkers and novel combination therapy of immune checkpoint inhibitors forAGC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Wenxiang Zhang ◽  
Xiangyi Kong ◽  
Bolun Ai ◽  
Zhongzhao Wang ◽  
Xiangyu Wang ◽  
...  

Tumor immune escape refers to the phenomenon in which tumor cells escape the recognition and attack of the body’s immune system through various mechanisms so that they can survive and proliferate in vivo. The imbalance of immune checkpoint protein expression is the primary mechanism for breast cancer to achieve immune escape. Cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) are critical immune checkpoints for breast cancer. Immune checkpoint inhibitors block the checkpoint and relieve its inhibition effect on immune cells, reactivate T-cells and destroy cancer cells and restore the body’s ability to resist tumors. At present, immunological checkpoint inhibitors have made significant progress in breast cancer immunotherapy, and it is expected to become a new treatment for breast cancer.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A310-A310
Author(s):  
Krishna Gunturu ◽  
Muhammad Awidi ◽  
Rojer Ranjit ◽  
Brendan Connell ◽  
Rachel Carrasquillo ◽  
...  

BackgroundICI revolutionized modern Oncology landscape and being utilized in metastatic to adjuvant and neo-adjuvant settings. As Oncologists, we are treating cancer patients with ICI every day, yet there is still a lot that is unknown about these drugs. We don’t have clear understanding of the efficacy and toxicity when sequencing one ICI for another. We conducted a retrospective review of real world data at Lahey Hospital and Medical Center to understand further and to pave path for prospective studies to understand this issue further to improve patient care.MethodsWe retrospectively reviewed Oncology patient charts who received ICI between January1, 2014 to December 18, 2018. Total 483 patients received ICI during this time frame and 22 of these patients received a second ICI either as monotherapy or in combination with other ICI or chemotherapy.ResultsA total of 22 patients received subsequent ICI after the initial ICI as showed in table 1. 15 of the 22 (68%) patients were transitioned from one ICI to another monotherapy. 11 of these patients were transitioned secondary to disease progression (73%), three had immune related adverse events and one was switched per standard of care. One patient had ICI re-challenge. Three patients had a transition from ICI monotherapy to combination ICI therapy. One patient went onto chemo-immunotherapy and 2 patients transitioned from combination ICI to chemo-immunotherapy.Abstract 284 Table 1Real world data of sequencing immune checkpoint inhibitors (ICI) after initial ICIConclusionsICI therapy is evolving and patients are being treated with multiple lines of ICI. In current practices, ICI is frequently being transitioned from cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1) classes or combined with chemotherapy or targeted therapy. It would be prudent to explore the effects of sequencing these medications either as a monotherapy or in combination with other therapies to better serve our patients and to prevent financial toxicity.


2020 ◽  
Vol 14 ◽  
pp. 117955492097636
Author(s):  
Ah-Reum Jeong ◽  
Edward D Ball ◽  
Aaron Michael Goodman

Treatment of cancer has transformed with the introduction of checkpoint inhibitors. However, the majority of solid tumor patients do not respond to checkpoint blockade. In contrast, the response rate to programmed cell death 1 (PD-1) blockade in relapsed/refractory classical Hodgkin lymphoma (cHL) is 65% to 84% which is the highest among all cancers. Currently, checkpoint inhibitors are only approved for cHL and primary mediastinal B-cell lymphoma as the responses to single-agent checkpoint blockade in other hematologic malignancies is disappointingly low. Various established biomarkers such as programmed cell death 1 ligand 1 (PD-L1) protein surface expression, mismatch repair (MMR) status, and tumor mutational burden (TMB) are routinely used in clinical decision-making in solid tumors. In this review, we will explore these biomarkers in the context of hematologic malignancies. We review characteristic 9p24.1 structural alteration in cHL and primary mediastinal B-cell lymphoma (PMBCL) as a basis for response to PD-1 inhibition, as well as the role of antigen presentation pathways. We also explore the reported frequencies of MMR deficiency in various hematologic malignancies and investigate TMB as a predictive marker.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1424
Author(s):  
Antonio Lopez-Beltran ◽  
Fernando López-Rios ◽  
Rodolfo Montironi ◽  
Sophie Wildsmith ◽  
Markus Eckstein

Immuno-oncology (IO) agents (anti–programmed cell death 1 (PD-1) and anti–programmed cell death-ligand 1 (PD-L1)) are approved as first- and second-line treatments for metastatic UC. PD-L1 expression levels in UC tumors help clinicians determine which patients are more likely to respond to IO therapies. Assays for approved IO agents use different antibodies, immunohistochemical protocols, cutoffs (defining “high” vs. “low” PD-L1 expression), and scoring algorithms. The robust control of pre-analytical and analytical standards is needed to obtain high-quality PD-L1 results. To better understand the status and perspectives of biomarker-guided patient selection for anti–PD-1 and anti–PD-L1 agents in UC, three workshops were held from December 2018 to December 2019 in Italy, Malaysia, and Spain. The primary goal was to develop recommendations for best practice approaches to PD-L1 testing in UC. Recommendations pertaining to the interpretation and reporting of the results of PD-L1 assays from experienced pathologists and oncologists from around the globe are included. A test request form for pathology laboratories was developed as a critical first step for oncologists/urologists to encourage communication between clinicians and pathologists, ensuring fast and high-quality test results. In this era of personalized medicine, we briefly discuss novel biomarkers being evaluated for IO agents in UC.


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