scholarly journals Toxicity of Immune-Checkpoint Inhibitors in Hematological Malignancies

2021 ◽  
Vol 12 ◽  
Author(s):  
Katarina Hradska ◽  
Roman Hajek ◽  
Tomas Jelinek
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Hematological Malignancies ◽  
Checkpoint Inhibitors ◽  
B Cell Lymphoma ◽  
Immune Checkpoint Blockade ◽  
Programmed Death ◽  
Anti Cancer ◽  
Programmed Death 1 ◽  
Insight Into

Immune checkpoint inhibitors (ICIs), especially those targeting the programmed-death 1 (PD-1) receptor and its ligands, have become indispensable agents in solid tumor anti-cancer therapy. Concerning hematological malignancies, only nivolumab and pembrolizumab have been approved for the treatment of relapsed and refractory classical Hodgkin lymphoma and primary mediastinal large B cell lymphoma to date. Nevertheless, clinical research in this field is very active. The mechanism of action of ICIs is based on unblocking the hindered immune system to recognize and eliminate cancer cells, but that also has its costs in the form of ICI-specific immune related adverse events (irAEs), which can affect any organ system and can even be lethal. In this article, we have reviewed all prospective blood cancer clinical trials investigating ICIs (both monotherapy and combination therapy) with available toxicity data with the purpose of determining the incidence of irAEs in this specific setting and to offer a brief insight into their management, as the use of immune checkpoint blockade is not so frequent in hemato-oncology.

scholarly journals Disparities in the Use of Programmed Death 1 Immune Checkpoint Inhibitors

2018 ◽  
Vol 23 (11) ◽  
pp. 1388-1390 ◽  
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

scholarly journals Immune checkpoint inhibitors in renal cell carcinoma

2017 ◽  
Vol 131 (21) ◽  
pp. 2627-2642 ◽  
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.

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

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.

scholarly journals Immunotherapy in urothelial cancer: recent data and perspectives

2018 ◽  
Vol 13 (4) ◽  
pp. 16-24 ◽  
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.

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab

2020 ◽  
pp. 107815522092154
Author(s):  
Nikhila Kethireddy ◽  
Steffi Thomas ◽  
Poorva Bindal ◽  
Prateek Shukla ◽  
Upendra Hegde
Keyword(s):  
Type 1 Diabetes ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Polymyalgia Rheumatica ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Close Monitoring ◽  
Programmed Death ◽  
Programmed Death 1

Introduction Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes. Case report We present a rare case of an elderly male on pembrolizumab who suffered from four autoimmune toxicities including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica likely catalyzed by age-related immune activation. Management and outcome: Immunotherapy was indefinitely stopped, and patient was started on steroids for the immune-related adverse events with complete resolution of polymyalgia rheumatica. Thyroid dysfunction resolved once he started thyroid replacement therapy. His diabetes is well controlled with insulin and is followed by endocrinology. He continues on prednisone for immune-mediated pneumonitis with a good response with regular monitoring via computed tomography scans and pulmonary consultation. Discussion Few cases wherein multiple toxicities are seen within one patient are reported. Aging appears to be a risk factor for immune-related adverse events. Aging is associated with an increased incidence of autoimmunity as programmed death-1 ligand expression represents an important mechanism that tissues use to protect from self-reactive effector T cells. Programmed death-1 blockade breaks this protective mechanism and enhances autoimmune diseases. Therefore, close monitoring and extreme vigilance is warranted while using immune checkpoint inhibitors including pembrolizumab as multiple toxicities can occur within a short span of infusion, especially in elderly individuals. Prompt discontinuation and the use of a multidisciplinary team are prudent to prevent further morbidity and mortality.

scholarly journals Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Allan Relecom ◽  
Maysaloun Merhi ◽  
Varghese Inchakalody ◽  
Shahab Uddin ◽  
Darawan Rinchai ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Benefit ◽  
Immune Checkpoint Blockade ◽  
Mechanisms Of Action ◽  
Checkpoint Blockade ◽  
Adaptive Resistance ◽  
Insight Into

AbstractImmune checkpoint inhibitors provide considerable therapeutic benefit in a range of solid cancers as well as in a subgroup of hematological malignancies. Response rates are however suboptimal, and despite considerable efforts, predicting response to immune checkpoint inhibitors ahead of their administration in a given patient remains elusive. The study of the dynamics of the immune system and of the tumor under immune checkpoint blockade brought insight into the mechanisms of action of these therapeutic agents. Equally relevant are the mechanisms of adaptive resistance to immune checkpoint inhibitors that have been uncovered through this approach. In this review, we discuss the dynamics of the immune system and of the tumor under immune checkpoint blockade emanating from recent studies on animal models and humans. We will focus on mechanisms of action and of resistance conveying information predictive of therapeutic response.

scholarly journals Prospects for combining immune checkpoint blockade with PARP inhibition

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Anping Li ◽  
Ming Yi ◽  
Shuang Qin ◽  
Qian Chu ◽  
Suxia Luo ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Parp Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Parp Inhibition ◽  
Cancer Immunity ◽  
Anti Cancer

Abstract The immunogenicity of a cancer cell is derived from accumulated somatic mutations. However, on the contrary to increased immunogenicity, anti-cancer immune response tends to be feeble. This impaired anti-cancer immunity could be attributed to multiple factors including loss of immunodominant epitopes, downregulation of major histocompatibility complex, and immunosuppressive microenvironment, as well as aberrant negative co-stimulatory signals. Immune checkpoint inhibitors block negative co-stimulatory signals such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, ultimately reactivating anti-cancer immunity. Immune checkpoint inhibitors elicit potent anti-cancer effect and have been approved for multiple cancers. Nevertheless, there still are significant potential improvements for the applications of checkpoint inhibitor, especially considering frequent resistance. Recent studies demonstrated that additional PARP inhibition could alleviate resistance and enhance efficacy of immune checkpoint blockade therapy via promoting cross-presentation and modifying immune microenvironment. We proposed that PARP inhibitors could enhance the priming and tumor-killing activities of T cell, boost the whole cancer-immunity cycle, and thereby improve the response to immune checkpoint blockade. In this review, we focused the latest understanding of the effect of PARP inhibitors on anti-cancer immunity and PARP inhibitors combining immune checkpoint blockade therapy. Moreover, we summarized the preclinical and clinical evidence and discussed the feasibility of this combination therapy in future clinical practice.

scholarly journals Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3301
Author(s):  
Maureen L. Drakes ◽  
Cheryl M. Czerlanis ◽  
Patrick J. Stiff
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Gynecologic Cancer ◽  
Immune Checkpoint Blockade ◽  
Gynecologic Cancers ◽  
Programmed Death 1 ◽  
Cancer Types ◽  
State Of Affairs

This review provides an update on the current use of immune checkpoint inhibitors (ICI) in female gynecologic cancers, and it addresses the potential of these agents to provide therapy options for disease management and long-term remission in advanced disease patients, where surgery, chemotherapy, and/or radiation fail to meet this goal. The topic of immune checkpoint inhibitors (ICI) blocking cytotoxic T lymphocyte associated protein-4 (CTLA-4) and the programmed death-1 (PD-1) axis has come to the forefront of translational medicine over the last decade for several malignancies. The text will focus primarily on a discussion of ovarian cancer, which is the most frequent cause of death of gynecologic cancers; endometrial cancer, which is the most often diagnosed gynecologic cancer; and cervical cancer, which is the third most common female gynecologic malignancy, all of which unfavorably alter the lives of many women. We will address the critical factors that regulate the outcome of these cancer types to ICI therapy, the ongoing clinical trials in this area, as well as the adverse immune responses that impact the outcome of patients given ICI regimens.

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