Pneumotox » Drug » Immune checkpoint inhibitors (ICI) - ICI combinatorial Rx

Immune checkpoint inhibitors (ICI) - ICI combinatorial Rx

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The manifold possible adverse effects from ICI in varied organs must be checked in every patient receiving these medications. AEs tend to occur with higher frequency with combo theray than when these agent are taken in isolation. Anti CTLA-4, anti-CD52, anti-PD1, anti-PDL-1 antibodies (PMID 23714523, 24904570, 25776466). For review of pulmonary and nonpulmonary AEs, and management guidelines see under PMID 26371282, 29442540. Can be fatal (PMID: 29735504). For review see PMID 32158597.

Last update : 17/03/2020

I.a Pneumonitis (ILD), acute and/or severe (may cause ARDS)

3

I.b Pneumonitis (ILD)

5

I.c Eosinophilic pneumonia (pulmonary infiltrates and eosinophilia)

1

I.d Organizing pneumonia pattern (an area or areas of consolidation on imaging)

4

I.e Acute eosinophilic pneumonia (AEP)

1

I.f Acute fibrinous organizing pneumonia (AFOP)

1

I.g Pulmonary fibrosis

1

I.u Relapsing or migrating pneumonitis/pneumonia (see also Id)

1

I.v Abnormal lung function/pulmonary physiology (PFTs) without necessarily imaging or clinical evidence

1

I.w Rapidly progressive ILD/pulmonary fibrosis (Hamman-Rich syndrome)

1

I.y Progression, acceleration or exacerbation of preexisting ILD/fibrosis

1

I.aa Delayed ILD, -pneumonitis, -fibrosis

2

I.ad Radiation recall pneumonitis

1

I.aj Shrinking lung syndrome

1

I.ax Chronic pneumonitis

1

II.b ARDS - Acute lung injury

1

II.d Pulmonary edema, cardiogenic

1

III.m Coagulopathy

1

IV.a Bronchospasm - Wheezing - Asthma

1

IV.c Obliterative bronchiolitis (a pattern consistent with) (see also IVn, XVx)

1

IV.n Obstructive airway dysfunction (see also IVc, XVx)

1

IV.y Eosinophilic airway disease (asthma, bronchitis, bronchiolitis)

1

V.a Pleural effusion (uni- or bilateral) (can accompany DI-LDs)

1

V.s Serositis - Polyserositis

1

VI.b Pulmonary arterial hypertension

3

VII.a Lymphadenopathy (intrathoracic)

1

VIII.t Vocal cord paresis/paralysis

1

IX.a Diaphragm/inspiratory muscle weakness/paralysis (w/wo ARF)

2

IX.d Respiratory failure from ventilatory depression (due to neuromuscular blockade/paralysis)

1

IX.r Myasthenia gravis - Myasthenic-like syndrome

3

IX.ab Guillain-Barré (or GB-like) syndrome (w/wo ARF)

1

IX.ac Myositis of the respiratory muscles (May lead to respiratory muscle paralysis)

1

X.a DRES syndrome - DRESS-like reaction

1

X.c Capillary leak syndrome (CLS)

1

X.d Lupus - Lupus syndrome (see also Vd)

2

X.e Autoimmunity-Autoimmune conditions (+ANA, +anti-ds-DNA, +ANCAs, other auto-Abs)

2

X.f Anaphylaxis-Anaphylactoid reaction (can be fatal)

2

X.g Hypersensitivity reaction (may manifest with fever and/or skin, throat or airway involvement)

3

X.h Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

1

X.j Myopathy-Myositis-Polymyositis (see also under Xba)

1

X.k Sarcoid-like granulomatosis (endo-/extrathoracic)

2

X.m Vascultis (pulmonary, extrathoracic or systemic)-ANCA status unknown or negative)

1

X.s Vasculitis, pulmonary (w/wo AH), extrapulmonary, systemic: ANCA-positive

1

X.u Multiple organ dysfunction/failure (MODS/MOF)

1

X.am Immune-related adverse effect/toxicity

1

X.an Cytokine release syndrome - Cytokine storm

1

X.aw Connective tissue disease

2

X.ay Polymyalgia rheumatica

1

XI.n Neutropenia, agranulocytosis (w/wo infection/sepsis)

1

XI.y Adrenal suppression

2

XI.ag Vertebral compression fracture

1

XI.au Graft vs. host disease in transplant recipients

1

XI.av Deterioration of graft function in SOT recipients

1

XI.ba Nonrespiratory AE of interest

5

XII.a Left or biventricular dysfunction/failure

1

XII.c Pericardial effusion (w/wo tamponade)

2

XII.d Myocarditis (can be fulminant)

2

XII.e Takotsubo (stress) cardiomyopathy

1

XII.g Coronary artery disease (acute) - Myocardial ischemia/infarction

2

XII.l Cardiac arrhythmias or dysrhythmias (AF, VT, VF, TdP)

2

XII.n Cardiovascular collapse - Cardiogenic shock - Hypotension

1

XII.s Heart block (bundle branch- or AV-)

1

XII.ai Cardiotoxicity

1

XII.ax Necrotizing myocarditis (w/o evidence for CAD)

1

XII.ba Sudden cardiac death

2

XV.a Path: NSIP-cellular pattern (see also Ia, Ib)

1

XV.b Path: Eosinophilic pneumonia (subacute or acute) (see also Ic)

1

XV.c Path: Organizing pneumonia (OP/BOOP) pattern (see also Id)

1

XV.d Path: Acute fibrinous organizing pneumonia (AFOP-pattern) (see also If)

1

XV.e Path: ILD with a granulomatous component (see also Im)

1

XV.f Path: Diffuse alveolar damage (DAD-pattern) (see also IL)

1

XV.l Path: Pulmonary fibrosis (not otherwise specified or unclassifiable)

1

XV.v Path: Micronodular organizing pneumonia/BOOP

1

XV.x Path: Acute/subacute bronchiolitis (see also IVc, IVi)

1

XV.ba Path: Granulomatous lymphadenopathy

1

XV.co Path: Foamy inclusions in alveolar macrophages and/or in other lung cells

1

XV.cp Path: Pneumocyte vacuolization

1

XVI.k Imaging: An area or areas of consolidation

1

XVI.v Imaging: Centrilobular micronodules (can be diffuse)

1

XVI.bh Imaging: F18-PET scan positive lympadenopathy

1

XVI.bt Imaging: A subsolid lung nodule or nodules

1

XVII.b Opportunistic pulmonary/systemic infections

1

XVII.c Aspergillosis, pulmonary (invasive, allergic [ABPA], or mycetoma)

1

XVII.e Pneumocystis jiroveci pneumonia

1

XVII.g Tuberculosis (pulmonary, pulmonary, extrapulmonary or disseminated). Reactivation or de novo

3

XVII.q Viral pneumonia

1

XVII.r Fungal infection (pulmonary/extrapulmonary)

1

XIX.a BAL: An excess proportion of lymphocytes

1

XIX.b BAL: An excess proportion of neutrophils

1

XIX.c BAL: An excess proportion of eosinophils

1

Diagnosing DIRD

1

Drug and radiation history

2

Drug singularity - Correct identification of the drug

3

Consistent timing of exposure v. onset of symptoms

4

Clinical, imaging, BAL, pathological pattern consistent with the specific drug

5

Careful exlusion of another cause

6

Remission of symptoms with removal of drug

7

Recurrence with rechallenge (rarely advisable)

8

Causality assessment

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