Nebenwirkungsmanagement in der Immunonkologie

2019 ◽  
Vol 144 (05) ◽  
pp. 346-353 ◽  
Author(s):  
Niels Reinmuth ◽  
Michael Bitzer ◽  
Barbara Deschler-Baier ◽  
Jürgen Fischer ◽  
Jonas Kuon ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Treatment Approach ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Case Reports ◽  
Oncological Treatment ◽  
Management Procedures ◽  
Adequate Management

AbstractThe immune oncological treatment approach uses immune checkpoint inhibitors to prevent tumor cells from shutting down the immune system, and thus from escaping immune response. Following the clinical success of immune checkpoint inhibitors, the number of approved immune oncological therapies continues to increase. Response rates and overall survival with anti-PD-1/PD-L1 and CTLA-4 blockade could be further improved by combining both treatment approaches. However, checkpoint inhibition is associated with a unique spectrum of side effects termed immune-related adverse events. These typically occur 3 to 6 months after treatment start and resolve with adequate management procedures if detected early on. Therefore, profound patient education, sensitizing and monitoring are mandatory. We describe in this article selected frequent and rare adverse events that are clinically relevant. Furthermore, using case reports, interdisciplinary experts share their practice-based experience in the management of frequent pneumonic, endocrine, and gastro-intestinal immune-related adverse events.

scholarly journals Central Nervous System Demyelination Associated With Immune Checkpoint Inhibitors: Review of the Literature

2020 ◽  
Vol 11 ◽  
Author(s):  
Marcos C. B. Oliveira ◽  
Marcelo H. de Brito ◽  
Mateus M. Simabukuro
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Cell Mediated Immune Response ◽  
Central Nervous System Demyelination

Immune checkpoint inhibitors (ICI) are a novel class of antineoplastic treatment that enhances immunity against tumors. They are associated with immune adverse events, and several neurological syndromes have been described, including multiple sclerosis and atypical demyelination. We performed a systematic literature review of case reports with neurological immune adverse events that presented with central nervous system demyelination, up to December 2019. We found 23 cases: seven with myelitis, four isolated optic neuritis, one neuromyelitis optica spectrum disorder, five multiple sclerosis, and six with atypical demyelination. Ipilimumab was the most frequently used ICI (11/23). The median time to develop symptoms from the onset of ICI was 6.5 weeks [range 1.0–43.0], and from last ICI dose was 14 days [range 0–161]. Anatomopathological examination was performed in four cases, with the finding of a T-cell mediated immune response. Outcomes were generally favorable after immunosuppression: 18 patients had improvement or a full recovery, three patients did not respond to treatment, three patients died, and in one, treatment was not reported. We describe the patients' clinical presentation, treatment administered, and outcomes. We further speculate on possible pathophysiological mechanisms and discuss potential treatments that may be worth investigating.

Endocrine adverse events related with immune checkpoint inhibitors: an update for clinicians

Immunotherapy ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 481-510 ◽  
Author(s):  
Maria V Deligiorgi ◽  
Mihalis I Panayiotidis ◽  
Dimitrios T Trafalis
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Future Perspective ◽  
Programmed Cell Death 1 ◽  
Diagnostic Work ◽  
Work Up

Designated as scientific breakthrough of current decade, immune checkpoint inhibitors attenuate the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1)/ligand 1 (PD-L1) pathways, depriving cancer cells of a key strategy of evasion from immunosurveillance. The reinvigoration of immune response translates into clinical success, inevitably entwined with a novel constellation of immune-related adverse events. The present review dissects the endocrine immune-related adverse events, emphasizing their unique profile featured by unpredictable onset, irreversibility, nonspecific symptoms, wide clinical spectrum and sophisticated diagnostic work-up. Guidelines advocate individualized decision-making process guided by clinicians' judgement. Future perspective should be governed by five principles – prevention, anticipation, detection, treatment, monitoring – aiming to gain the optimal profit diminishing immunotoxicity.

scholarly journals Management of rheumatic complications of ICI therapy: a rheumatology viewpoint

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_7) ◽  
pp. vii49-vii58 ◽  
Author(s):  
Jan Leipe ◽  
Xavier Mariette
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Standard Of Care ◽  
Immunosuppressive Drugs ◽  
Anti Inflammatory

Abstract Since immune checkpoint inhibitors became the standard of care for an increasing number of indications, more patients have been exposed to these drugs and physicians are more challenged with the management of a unique spectrum of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors. Those irAEs of autoimmune or autoinflammatory origin, or both, can involve any organ or tissue, but most commonly affect the dermatological, gastrointestinal and endocrine systems. Rheumatic/systemic irAEs seem to be less frequent (although underreporting in clinical trials is probable), but information on their management is highly relevant given that they can persist longer than other irAEs. Their management consists of anti-inflammatory treatment including glucocorticoids, synthetic and biologic immunomodulatory/immunosuppressive drugs, symptomatic therapies as well as holding or, rarely, discontinuation of immune checkpoint inhibitors. Here, we summarize the management of rheumatic/systemic irAEs based on data from clinical trials but mainly from published case reports and series, contextualize them and propose perspectives for their treatment.

scholarly journals IMMU-04. IMMUNE-RELATED ADVERSE EVENTS STRONGLY PREDICT SUPERIOR OUTCOMES IN BRAIN METASTASES PATIENTS RECEIVING LOCAL TREATMENT AND IMMUNE CHECKPOINT INHIBITORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii105-ii105
Author(s):  
Alexander Hulsbergen ◽  
Asad Lak ◽  
Yu Tung Lo ◽  
Nayan Lamba ◽  
Steven Nagtegaal ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Adverse Events ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Local Treatment ◽  
Sensitivity Analyses ◽  
Immortal Time Bias ◽  
The Brain

Abstract INTRODUCTION In several cancers treated with immune checkpoint inhibitors (ICIs), a remarkable association between the occurrence of immune-related adverse events (irAEs) and superior oncological outcomes has been reported. This effect has hitherto not been reported in the brain. This study aimed to investigate the relation between irAEs and outcomes in brain metastases (BM) patients treated with both local treatment to the brain (LT; i.e. surgery and/or radiation) and ICIs. METHODS This study is a retrospective cohort analysis of patients treated for non-small cell lung cancer (NSCLC) BMs in a tertiary institution in Boston, MA. Outcomes of interest were overall survival (OS) and intracranial progression-free survival (IC-PFS), measured from the time of LT. Sensitivity analyses were performed to account for immortal time bias (i.e., patients who live longer receive more cycles of ICIs and thus have more opportunity to develop an irAE). RESULTS A total of 184 patients were included; 62 (33.7%) were treated with neurosurgical resection and 122 (66.3%) with upfront brain radiation. irAEs occurred in 62 patients (33.7%). After adjusting for lung-Graded Prognostic Assessment, type of LT, type of ICI, newly diagnosed vs. recurrent BM, BM size and number, targetable mutations, and smoking status, irAEs were strongly associated with better OS (HR 0.33, 95% CI 0.19 – 0.58, p < 0.0001) and IC-PFS (HR 0.41; 95% CI 0.26 – 0.65; p = 0.0001). Landmark analysis including only patients who received more than 3 cycles of ICI (n = 133) demonstrated similar results for OS and IC-PFS, as did sensitivity analysis adjusting for the number of cycles administered (HR range 0.36 – 0.51, all p-values < 0.02). CONCLUSIONS After adjusting for known prognostic factors, irAEs strongly predict superior outcomes after LT in NSCLC BM patients. Sensitivity analysis suggests that this is unlikely due to immortal time bias.

scholarly journals Rethinking immune checkpoint blockade: ‘Beyond the T cell’

2021 ◽  
Vol 9 (1) ◽  
pp. e001460 ◽  
Author(s):  
Xiuting Liu ◽  
Graham D Hogg ◽  
David G DeNardo
Keyword(s):  
Immune System ◽  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

The clinical success of immune checkpoint inhibitors has highlighted the central role of the immune system in cancer control. Immune checkpoint inhibitors can reinvigorate anti-cancer immunity and are now the standard of care in a number of malignancies. However, research on immune checkpoint blockade has largely been framed with the central dogma that checkpoint therapies intrinsically target the T cell, triggering the tumoricidal potential of the adaptive immune system. Although T cells undoubtedly remain a critical piece of the story, mounting evidence, reviewed herein, indicates that much of the efficacy of checkpoint therapies may be attributable to the innate immune system. Emerging research suggests that T cell-directed checkpoint antibodies such as anti-programmed cell death protein-1 (PD-1) or programmed death-ligand-1 (PD-L1) can impact innate immunity by both direct and indirect pathways, which may ultimately shape clinical efficacy. However, the mechanisms and impacts of these activities have yet to be fully elucidated, and checkpoint therapies have potentially beneficial and detrimental effects on innate antitumor immunity. Further research into the role of innate subsets during checkpoint blockade may be critical for developing combination therapies to help overcome checkpoint resistance. The potential of checkpoint therapies to amplify innate antitumor immunity represents a promising new field that can be translated into innovative immunotherapies for patients fighting refractory malignancies.

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