Managing Immunotherapy Related Organ Toxicities: A Practical Guide

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Certain organ toxicities can be severe and life-threatening. Therefore, it is crucial to recognize these disease entities early on to provide prompt and effective treatments to improve the quality of patient care, and enable the continuation of cancer therapy long-term. A clinical handbook with a particular focus in this field is lacking.

This handbook focuses on the comprehensive, systematic review of clinical aspects of immunotherapy-induced toxicities in 15 major organ systems. The organs covered include endocrine, eye, gut, heart, kidney, liver, lung, muscular-skeletal, neuro, pancreas and skin etc. A unique feature about this book is the inclusion of perspectives from Anesthesiology, Infectious Disease, and Pathology besides specific organ toxicity management.

The contributors are a group of experts offering routine clinical care to patients with most complex and refractory toxicity conditions, conducting pioneering research, and providing the guidance for the clinical practice to the peers and trainees in the field. The topics of each chapter include incidence, clinical presentations, evaluation, management, and long term follow up of each disease entity. There is also a simplified management algorithm or table illustrated in each chapter as well as audio PowerPoint slide deck to provide straightforward general instruction on the evaluation and treatment.


Author(s): Yinghong Wang
Publisher: Springer
Year: 2022

Language: English
Pages: 332
City: Cham

Preface
Introduction
Contents
Contributors
Chapter 1: Anesthesia
General Recommendations
Organ-Specific Treatment Strategies
References
Chapter 2: Cardiology (Heart)
Available Immune Checkpoint Inhibitors
Cardiac Side Effect Profile of Immune Checkpoint Inhibitors
Mechanisms of Myocardial Toxicity
ICI-Associated Myocarditis
Timing Onset of Myocarditis
Diagnostic Testing Considerations in ICI-Associated Myocarditis
Troponin
Natriuretic Peptide
Electrocardiogram (ECG)
Echocardiography
Cardiac Magnetic Resonance (CMR) Imaging
Endomyocardial Biopsy (EMB)
Management
Advanced Management
Conclusion
References
Chapter 3: Dermatology (Skin)
Epidemiology
Clinical Characteristics
Morbilliform/Maculopapular Rash (MPR)
Pruritus
Eczematous Dermatitis
Urticaria
Lichenoid/Lichen Planus-Like Eruption
Psoriasiform Dermatitis
Vitiligo
Granulomatous Dermatitis
Xerosis
Autoimmune Bullous Disorders
Severe Cutaneous Adverse Reactions
Erythema Multiforme (EM)
Neutrophilic Dermatoses
Sweet’s Syndrome (Acute Febrile Neutrophilic Dermatosis)
Pyoderma Gangrenosum
Follicular Eruptions
Rheumatologic Disease
Dermatomyositis and polymyositis
Mucosal Toxicities
Hair Toxicities
Nail irCAEs
Less Common irCAEs
Grover’s Disease
Keratoacanthoma/Cutaneous Squamous Cell Carcinoma
Evaluation
Diagnostic Tests for Specific irCAEs
Bullous Pemphigoid
Dermatitis Herpetiformis
Pemphigus Vulgaris-Like Lesions
Urticaria
Hair Toxicities
Rheumatologic Diseases
Treatment
Treatment Pearls
Pruritus
Eczematous
Urticaria
Lichenoid
Psoriasiform
Vitiligo
Bullous Pemphigoid
Alopecia
Mucosal Toxicities (Including Lichenoid Eruptions)
Nail Toxicities
Neutrophilic Dermatoses
Granulomatous
SCARs
Erythema Multiforme
Sarcoidosis
Treatment Recommendations
Long-Term Complication and Follow-Up
References
Chapter 4: Endocrine
Introduction
Checkpoint Inhibitor-Induced Hypophysitis
Epidemiology
Clinical Characteristics
Evaluation
Treatment
Long-Term Complications and Follow-Up
Thyroid Dysfunction
Epidemiology
Clinical Characteristics
Evaluation
Treatment
Long-Term Complications and Follow-Up
Primary Adrenal Insufficiency
Epidemiology
Clinical Presentation
Treatment
Checkpoint Inhibitor-Induced Diabetes
Epidemiology
Clinical Characteristics
Evaluation
Treatment
Long-Term Complications and Follow-Up
References
Chapter 5: Gastroenterology (GI)
Epidemiology and Risk Factors
Type of ICI Agent
Type of Cancer
The Patient
Clinical Presentation and Evaluation
Clinical Presentation
Clinical Evaluation
Biochemical and Stool Evaluation
IMC, Infections, and Its Management
Imaging
Endoscopic Evaluation
Histologic Evaluation
Treatment of IMC
Recurrence of IMC
Surveillance
Maintenance Therapy
IMC and Its Impact on Cancer Outcomes
Future Direction and Scope
Conclusion
Immune-Mediated Upper GI Toxicity (from the Mouth to the Ligament of Treitz)
ICI Mucositis (IMM)
ICI-Related Esophagitis
ICI-Related Gastroenteritis
References
Chapter 6: Hematology
Autoimmune Hemolytic Anemia
Epidemiology
Clinical Characteristics
Evaluation
Treatment
ICI-Related Warm AIHA
ICI-Related Cold AIHA
Long-Term Complications and Follow-Up
Immune Thrombocytopenic Purpura
Epidemiology
Clinical Characteristics
Evaluation
Treatment
Long-Term Complications and Follow-Up
Autoimmune Neutropenia
Epidemiology
Clinical Characteristics
Evaluation
Treatment
Long-Term Complication and Follow-Up
Bone Marrow Failure Syndromes
Epidemiology
Clinical Characteristics
Evaluation
Treatment
Long-Term Complications and Follow-Up
Macrophage Activation Syndrome/Hemophagocytic Lymphohistiocytosis
Epidemiology
Clinical Characteristics
Evaluation
Treatment
Long-Term Complications and Follow-Up
Thrombophilia and Hemostasis Complications
Epidemiology
Clinical Characteristics
Evaluation
Treatment
Long-Term Complications and Follow-Up
References
Chapter 7: Hepatology (Liver and Bile Duct)
Introductions
Nomenclature
Epidemiology
Pathophysiology
Clinical Characteristics
Evaluation
Initial Assessment
Imaging
The Role of Liver Biopsy and Histopathologic Features
Management and Treatment Options
Summary of Initial Management Recommendations
Commentary on Steroid Treatment Strategies
Cholangiopathic Phenotypes: Immune-Mediated Cholangiopathy or Cholangiohepatitis
Adjunctive Treatments
Kinetics of Biochemical Improvement
Approach to Suspected or Confirmed IMH in the Context of Intrahepatic Primary Tumors or Metastatic Liver Lesions
Outcomes and Follow-Up
Overview
The Risk of Relapse or Flare During the Management of IMH
Re-challenging with ICI After Recovery from Grade 3–4 IMH
Mortality in IMH
Evaluation for Pre-existing Liver Disease and Viral Infections Before Initiating ICI
Conclusions
References
Chapter 8: Infectious Diseases
Overview
Background
Sources of Infection
Impact of the Underlying Malignancy
Risk Factors
Timing of Infection (Prior, During, and After Checkpoint Inhibitor Therapy)
Microbiome Signatures Associated with Response Cancer Therapy and ICIs-Related Toxicity
Use of Antibiotics in Patients on ICIs
Screening for Infectious Diseases Prior to Initiation of ICIs and Potential Use of Immunosuppressants
Antimicrobial Prophylaxis
Indications
Management and Outcomes of Common Infections in the Patient Receiving ICIs
Infections Related to ICIs Use
Combination Therapy Versus Monotherapy
As Adjuvants to Chemotherapy
Overlap Between Clinical Presentation of Infection and Immune Adverse Events
Organ-Specific Considerations
Pneumonitis
Colitis
Encephalitis
Sepsis
Mucositis
Infections that Can Trigger ICIs Toxicity
Infection with SARS-CoV-2 in Patients Receiving ICIs
Vaccination of Patients Receiving ICIs
Knowledge Gaps and Other Areas of Uncertainty (Table 8.4)
Adjuvant Use of ICIs to Treat Infection
Biomarkers That Can Help Differentiate irAEs from Infection
Tailoring Immunosuppression to Least Dose Effective
Objective Markers of Net Immunosuppression
The Need for Antimicrobial and Microbiome Stewardship
References
Chapter 9: Nephrology (Kidney)
Introduction
Incidence and Risk Factors
Clinical Characteristics of Renal Adverse Events
Electrolyte and Acid-Base Disturbances
Renal Pathologies Associated with irAEs
ATIN
Proposed Mechanisms of ATIN
ATN
GN
Re-Challenge of ICI in GN Cases
Proposed Mechanisms of Glomerular Diseases and Vasculitis
ICI Use in Solid Organ Transplant Recipients
Long-Term Complications and Follow-Up
References
Chapter 10: Neurology
Epidemiology
Clinical Characteristics
Evaluation
Treatment Principles
Long-Term Complication and Follow-Up
References
Chapter 11: Ophthalmology (Eye)
Introduction
Epidemiology
Mechanism of IRAEs
Clinical Characteristics
Conjunctiva/Cornea
Keratoconjunctivitis
Peripheral Ulcerative Keratitis
Sclera and Episclera
Episcleritis
Scleritis
Uvea (Choroid, Ciliary Body, Iris)
Uveitis
Choroidal Neovascularization
Retina/Optic Nerve
Cystoid Macular Edema
Retinal Vasculitis
Retinal Detachment
Optic Neuropathy
Orbital Inflammation
Orbital Inflammatory Syndrome
Thyroid Eye Disease
Giant Cell Arteritis
Myasthenia Gravis
Evaluation
Treatment Algorithm
Long-Term Complication and Follow-Up
Prognosis
Summary
References
Chapter 12: Pancreas and Gallbladder
Immune Checkpoint Inhibitor-Mediated Pancreas Injury (ICI-PI)
Definition and Background
Grading and Severity
Epidemiology and Risk Factors
Clinical Presentation and Management
Overall Survival and Prognosis
Is ICI-PI a Third Type of Autoimmune Pancreatitis (AIP)?
Immune Checkpoint Inhibitor-Mediated Cholecystitis (ICICC)
References
Chapter 13: Pathology
Introduction
Pathological Features of ICIs-Induced Toxicities by Organ/System
Luminal Gastrointestinal Tract Toxicity
Hepatobiliary Toxicity
Pancreatic Toxicity
Pulmonary Toxicity
Cardiac Toxicity
Neuromuscular Toxicity
Renal Toxicity
References
Chapter 14: Pulmonology (Lung)
ICI Pneumonitis
Introduction
Clinical Presentation
Diagnostic Approach
Imaging Patterns
Pulmonary Function Testing
Bronchoscopy
Lung Biopsy
Assessment of Severity
Epidemiology and Risk Factors
Type of ICI
Monotherapy vs. Combination Therapy
Prior Treatment History
Prior Radiation Therapy
Type of Malignancy
Tumor Mutational Burden
Prior Lung Disease
Treatment
Corticosteroids
Steroid-Refractory Pneumonitis
IVIg
Infliximab
Mycophenolate Mofetil
Cyclophosphamide
Aviptadil
Outcomes After ICIP
ICI Re-challenge
ICI Pleural Effusions
Sarcoidosis-Like Reactions
ICI-Related Eosinophilic Lung Diseases
Conclusion
References
Chapter 15: Rheumatology (Arthritis and Myositis)
Articular irAE
Epidemiology
Clinical Characteristics
Management
Long-Term Complications and Follow-Up
Muscular irAEs
Epidemiology
Clinical Characteristics
Management
Long-Term Complications and Follow-Up
Polymyalgia Rheumatica-Like Syndrome
Epidemiology
Clinical Characteristics
Management
Long-Term Complications and Follow-Up
Conclusion
References
Index