With the increasing use of immune checkpoint inhibitors (ICI) across various cancers, the trends for indication at earlier stages, and the use of combination immunotherapy, the frequency of ICI-induced immune-related adverse events (irAE) is expected to grow substantially. Management of these irAE is challenging as it requires not only consideration of the toxicity but also risk-benefit ratios with respect to the primary cancer. Several rheumatic irAE have been reported with ICI therapy including arthritis, myositis, polymyalgia-like syndromes, sicca/Sjogren-like manifestations, and several other less common systemic autoimmune features commonly associated with connective tissue disease.
This handbook provides clinicians with a comprehensive overview of the management of rheumatic irAE that develop from cancer immunotherapy. It focuses on the irAE seen with ICI, the most frequently used agents in treating cancer. It provides an overview of cancer immunology, immunotoxicity, and immunotherapies such as ICI, cytokine-based therapy, and CART. It examines the epidemiology, clinical manifestations, diagnosis, differential diagnosis, and treatment of a variety of rheumatic immune-related adverse events arising from these therapies. Chapters also cover cancer immunotherapy in patients with preexisting rheumatic diseases such as inflammatory arthritis and other connective tissue disorders. The book helps clinicians to distinguish the current types of cancer immunotherapy and general toxicity patterns, recognize and diagnose rheumatic clinical syndromes, understand the pathogenesis of irAE, and consider risk–benefit ratios when managing patients with rheumatic irAE.
Rheumatic Diseases and Syndromes Induced by Cancer Immunotherapy is an essential resource for physicians and related professionals, residents, fellows, graduate students and nurses alike in rheumatology, clinical immunology, oncology, and internal medicine.
Author(s): Maria E. Suarez-Almazor, Leonard H. Calabrese
Edition: 1
Publisher: Springer
Year: 2021
Language: English
Pages: 377
Introduction
Contents
Contributors
Part I: Introduction
Chapter 1: Cancer Immunology and the Evolution of Immunotherapy
Cancer Immunology: Immunoediting Hypothesis
Elimination
Equilibrium
Escape
Cancer Immunotherapy
Immune Checkpoint Inhibitors
Cytokines
Cancer Vaccines
Adoptive Cell Therapy
Epigenetic Drugs
Future of Cancer Immunotherapy
References
Chapter 2: Cancer Immunotherapy: Overview of Immune Checkpoint Inhibitors
CTLA-4 Inhibitors
PD-1 and PD-L1 Inhibitors
PD-1 Inhibitors
Pembrolizumab
Nivolumab
Cemiplimab
PDL-1 Inhibitors
Atezolizumab
Durvalumab
Avelumab
Combination Immunotherapy
References
Chapter 3: Immunopathogenesis of Immune-Related Adverse Events from Cancer Immunotherapy
Autoimmunity or Autoinflammation?
Putative Mechanisms of Immunopathogenesis
Preclinical Models
Lessons from Primary Immunodeficiency States
Drugs and Disease Effects
Basic Mechanisms of Autoimmunity and Autoinflammation for Checkpoint Inhibitors
Experimental Construct for the Evolution of Autoimmune Diseases
Proposed Immunologic Pathways Contributing to irAEs
Generalized Immune Activation
Direct Off-Target Effects of ICIs
Preexisting Asymptomatic Autoimmunity
Off-Target Effects of T Cell-Mediated Immunity
Genetic and Environmental Factors
Clinical Implications and Summary
References
Part II: Immune-Related Adverse Events with Immune-Checkpoint Inhibitors
Chapter 4: Immune-Related Adverse Events with Immune Checkpoint Inhibitors: Arthritis
Introduction
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Laboratory Testing
Imaging
Differential Diagnosis
Management
Immunosuppression and Tumor Response
Prognosis
Conclusions and Future Directions
Case Study
References
Chapter 5: Immune-Related Adverse Events with Immune Checkpoint Inhibitors: Polymyalgia Rheumatica
Introduction
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
Conclusions and Future Directions
Case Study
References
Chapter 6: Myositis
Introduction
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
Conclusions and Future Directions
Case Study
References
Chapter 7: Sicca Syndromes
Introduction
Epidemiology
Pathogenesis
Histopathology
Literature Review of Reported Cases
Subsets of ICI-Induced Sicca
De novo Development of Oral and/or Ocular Dryness Without Systemic Manifestations
De Novo Development of Oral and/or Ocular Dryness with Systemic Manifestations
Flare of a Recognized Preexisting Rheumatic Disease, Associated with Ocular and Oral Dryness
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
ICI-Induced Sicca Without Systemic Symptoms
ICI-Induced Sicca with Systemic Symptoms
ICI-Induced Sicca in the Setting of Preexisting Rheumatic Disease
Conclusions and Future Directions
Case Study
References
Chapter 8: Sarcoidosis
Introduction
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Differential Diagnosis
Drug-Induced Pneumonitis
Cancer Progression
Infection
Management
Prognosis
Conclusions and Future Directions
Case Study
References
Chapter 9: Miscellaneous Rheumatic Syndromes
Introduction
Vasculitis
Large Vessel Vasculitis
Vasculitis of the Nervous System
Other Vasculitides
Systemic Lupus Erythematosus
Scleroderma
Eosinophilic Fasciitis
Conclusions and Future Directions
References
Chapter 10: Non-Rheumatic Immune-Related Adverse Events
Introduction
Neurologic Immune-Related Adverse Events
Acute Encephalitis
Peripheral Neuropathy and Guillain-Barre Syndrome
Myasthenia Gravis
Ophthalmic irAEs: Uveitis
Pulmonary irAEs: Pneumonitis
Gastrointestinal irAEs
Colitis
Immune-Related Hepatitis
Immune-Related Pancreatitis
Hematologic irAEs: Immune-Related Thrombocytopenia
Cardiovascular irAEs: Myocarditis and Pericarditis
Dermatologic irAEs: Maculopapular Dermatitis and Pruritus
Renal irAEs
Endocrine irAEs: Hypophysitis, Hypothyroidism, and Type 1 Diabetes Mellitus
Conclusions and Future Directions
References
Chapter 11: Immune-Related Adverse Events with Other Cancer Immunotherapies
Adoptive Cell Therapies: Chimeric Antigen Receptor T-Cell (CAR-T) Therapy
Cytokine Release Syndrome
Immune Effector Cell-Associated Neurotoxicity Syndrome
Cytokines
Recombinant Interferon-Alpha
Recombinant Interleukin-2 Therapy
Vascular Leak Syndrome
Myocarditis
Vaccines
Sipuleucel-T
Mycobacterium bovis Bacillus Calmette-Guérin (BCG)
Conclusions and Future Directions
References
Part III: Cancer Immunotherapy in Patients with Pre-existing Rheumatic Diseases
Chapter 12: Cancer Immunotherapy in Patients with Preexisting Inflammatory Arthritis
Introduction
Epidemiology
Rheumatoid Arthritis
Spondyloarthritis
Pathogenesis
Case Study
Management
References
Chapter 13: Cancer Immunotherapy in Patients with Preexisting Rheumatic Diseases: Other Rheumatic Autoimmune Diseases
Introduction
Epidemiology
Clinical Manifestations
Diagnosis
Management
General Considerations
Baseline Evaluation and Immunosuppressive Regimen
Flare and/or irAE Management
Conclusion
Case Study
References
Part IV: General Principles of Management
Chapter 14: Management of Rheumatic Immune-Related Adverse Events (irAEs): General Principles
Introduction
Guidelines
ASCO/SITC Guidelines
General Principles of Immunosuppression for Rheumatic irAEs: Targeted Therapies
Anti-TNF-Directed Therapies
Anti-IL-6-Directed Therapies
Anti-IL-1-Directed Therapies
Anti-IL-17-Directed Therapies
Anti-B-Cell-Directed Therapies
Janus Kinase Inhibitors (Jak-i)
Abatacept
Conclusions
References
Chapter 15: Benefit-Risk Considerations
Evaluating the Potential Benefits and Risks of Therapies
Benefits
Types of Benefits
Magnitude of Effect
Duration
Likelihood of Patients Experiencing a Benefit
Medical Need
Patient Values and Preferences
Harms
Types of Harms
Severity and Impact
Duration
Likelihood of Risk
Patient Tolerance of Risk and Uncertainty
Multidisciplinary Approach
Case Studies
Conclusions and Future Directions
References
Chapter 16: Patient Education and Shared Decision-Making
Patient Education
Learning Needs
Education Strategies
Assessment of Health Literacy
Patients’ Values
Shared Decision-Making
Forms of Health Communication
Discredit False Information
Discussing Immune-Related Adverse Events Management Plans
Conclusions and Future Directions
References
Index
