Table 2 Risk factors for irAE. irAE, immune-related adverse event; IL-6, interleukin-6; NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma; ILD, interstitial lung disease; GI, gastrointestinal; RLC, relative lymphocyte count; RNC, relative neutrophil count; REC, relative eosinophil count; CEACAM1, carcinoembryonic antigen cell adhesion molecule 1; AEC, absolute eosinophil count; DM, diabetes mellitus

Body Composition Parameters

Low muscle attenuation

Melanoma

CTLA-4 inhibitor

Grade III-IV irAE include rash, diarrhoea, colitis, hypotituitarism, arthritis etc.

[52]

Sex

Female

Melanoma

CTLA-4 inhibitor

Grade III-IV irAE include pruritus, diarrhea, hypophysitis etc.

[53]

Tumour histology

Melanoma compared to NSCLC

CTLA-4 inhibitor & PD-(L)1 inhibitor

↑Risk of GI & skin irAE↓Risk of penumonitis

[54]

Melanoma compared to RCC

CTLA-4 inhibitor & PD-(L)1 inhibitor

↑Risk of dermatitis, arthritis & myalgia↓Risk of pneumonitis & dyspnea

RCC compared to melanoma

CTLA-4 inhibitor & PD-(L)1 inhibitor

↑Risk of pneumonitis & dyspnea

Past medical history

pre-existing AID

Solid tumors

CTLA-4 inhibitors & PD-(L)1 inhibitors

Likely increase risk of irAE, particularly in patients on immuno-suppressive therapy

[55,56,57,58,59,60,61,62]

HIV infection

Solid tumors

CTLA-4 inhibitors & PD-(L)1 inhibitors

Not increased

[63,64,65,66,67,68,69,70,71]

Concurrent or sequential treatment

High dose radiotherapy

Solid tumors

CTLA-4 inhibitors & PD-(L)1 inhibitors

Likely increase risk of irAE, particularly in patients receiving higher radiation dose

[72,73,74,75,76]

Vemurafenib

Melanoma

CTLA-4 inhibitors

Hepatic toxicity

[77]

Trametinib + Vemurafenib

Melanoma

CTLA-4 inhibitors

Severe colitis

[78]

BRAF & MEK inhibitor

Melanoma

PD-(L)1 inhibitors

Hepatic toxicityPyrexia

[79, 80]

Crizotinib

NSCLC

PD-(L)1 inhibitors

Hepatic toxicity

[81, 82]

EGFR-TKI except osimertinib

NSCLC

PD-(L)1 inhibitors

Not increased

[83, 84]

Osimertinib prior to ICIs

NSCLC

PD-(L)1 inhibitors

Grade 3–4 irAEs include pneumonitis, hepatitis, colitis

[85]

Osimertinib after ICIs

NSCLC

PD-(L)1 inhibitors

Increased rate of ILD

[85,86,87]

Antibodies

Pretreatment anti-thyroid antibody

NSCLC

PD-(L)1 inhibitors

Thyroid dysfunction

[32, 33]

Pre-treatment rheumatoid factor

Skin reactionAmyasthenia

[32]

Cytokine assays

↑baseline IL-17

Melanoma

CTLA-4 inhibitors

Grade 3 colitis

[88]

↓IL-10 after treatment

Urothelial carcinoma

CTLA-4 inhibitors

ischemic papillopathy & optic neuritis

[89]

↓IL-10 and↑IL-2 after treatment

Melanoma

CTLA-4 inhibitors

irAE

[90]

↑baseline IL-6(P<0.05)

Melanoma

CTLA-4 inhibitors

Grade III-IV irAE include rash, diarrhoea, colitis, hypotituitarism, arthritis etc.

[53]

↓Baseline IL-6, IL-8, &sCD25

Melanoma

CTLA-4 inhibitors

Colitis

[91]

↑IL-6 after treatment

Melanoma

PD-(L)1 inhibitor

Cutaneous irAE

[92]

↓Baseline CXCL9, CXCL10, CXCL11 and CXCL19;↑Post-treatment CXCL9 and CXCL10;

Solid tumors

PD-(L)1 inhibitor & CTLA-4 inhibitor

Pneumonitis, thyroid, arthritis, dematitis, etc.

[93]

↑Circulating sCD163

Melanoma

PD-(L)1 inhibitor

irAE

[94]

↑Baseline sCTLA-4 level

Melanoma

CTLA-4 inhibitor

Gastrointestinal irAE

[95]

Blood cells

↑WBC↓RLC↑RNC

Melanoma

PD-(L)1 inhibitor

GI irAEPulmonary irAE

[96]

↑CD177 & CEACAM1 (neutrophil-activation markers)

Melanoma

CTLA-4 inhibitor

GI irAE

[97]

ALC > 2000;↑Baseline AEC

Solid tumors

PD-(L)1 inhibitor

irAE include rash, colitis, hepatitis, pneumonitis, etc.

[98]

↑baseline AEC at and REC after treatment

Melanoma

PD-(L)1 inhibitor

Endocrine irAEs

[99]

Circulating T cells repertoire

prostate cancer

CTLA-4 inhibitor

IrAEs

[100]

Clonal expansion of CD8 T cells clones in peripheral blood

prostate cancer

CTLA-4 inhibitor

IrAEs?

[101]

Gut Microbiome

Faecalibaterium and other firmicutes

Melanoma

CTLA-4 inhibitor

Colitis

[91]

B.fragilis and Burkholderia cepacia

murine sarcoma

CTLA-4 inhibitor

↓ Intestinal irAE

[43]

Bacteroidetes phylum

Melanoma

CTLA4 inhibitor

↓ colitis

[45]

Genetic Variability

Predominance of HLA-DR4

Solid-organ cancer

PD-(L)1 inhibitor

diabetes

[102]

Homozygous variant of PDCD1 804 C>T(rs2227981)

NSCLC

PD-(L)1 inhibitor

↓ irAEs

[103]