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. 2022 Apr 26;13:779691. doi: 10.3389/fimmu.2022.779691

Table 1.

Risk factors and biomarkers for irAE incidence.

Factor High risk of irAE (odds ratio)
Patient-specific Demographics and Social history

  • Age < 60 years (1.70) (30)

  • Men in PD-1/PD-L1 (0.81) (30–32)

  • Women in CTLA4 (1.5) (31, 33, 34)

  • ECOG ≥ 2 (3.79) (35)

  • Smoking of ≥ 50 pack-years (3.19) or current smoker (HR-2.26) (34–36)

  • Higher body mass index (for ≥ 23 kg/m2, OR=2.62; for ≥ 25kg/m2, OR=1.08) (37–39)

  • Sarcopenia (5.34) (40)

  • Low muscle mass (3.57) (40)
Medical history

  • Autoimmune disease (2.57) (41–43).

  • Allergies (1.48) (food, drug, or contrast) (44)

  • Interstitial lung diseases (6.6), chronic obstructive pulmonary disease (2.79), asthma (OR = 2.82); history of thoracic radiation (3.3) (27, 45–49)

  • Hypertension (4.3)

  • Coronary artery disease, heart failure, myocardial infarction are more prone to cardiac-irAE (50)*

  • Chronic Kidney disease (eGFR < 30 ml/min) (1.9) (51)
Medication history

  • PPI (OR = 2.85) and NSAID (OR = 1.36) (51–56)

  • Diuretics (OR = 4.3) and ACEI/ARD (OR = 2.9) (57)

  • Anthracyclines, HER2 inhibitors, and VEGF TKIs (50)*

  • Antibiotics (58)

  • Vitamin D deficiency* (59, 60)

  • Influenza vaccinations*1 (61)
Tumor-specific Non-specific

  • Higher disease burden (≥ 2 metastatic sites, OR = 8.62) (24, 62)

  • Higher tumor mutational burden2 (63)
Melanoma3

  • High risk for diarrhea (1.9/1.3), rash (1.8/1.6), pruritis (2.4/1.5), colitis (4.2/not reported) (21, 34)

  • Low risk for pneumonitis (0.4/0.3)
Breast cancer

  • Higher fatal adverse events in patients with PD-1 (3.1%)4 (25)
AML/MDS

  • High risk for dermatitis and hepatitis* (64)
Agent-specific CTLA4 inhibitors

  • In combination with PD-1 (vs PD-1/PD-L1) (1.53; 1.88) 5 (22, 65–67)

  • Monotherapy (vs PD-1/PD-L1) - Organ-nonspecific (2.02); Colitis (8.7); hypophysitis (6.5); and rash (2) (21)
PD-1 inhibitors

  • Pneumonitis (6.4), arthralgia, vitiligo (3.5), and hypothyroidism (4.3) vs. CTLA4 (21)
Organ-nonspecific

  • High risk when combined with chemotherapy (OR for grade I-V, 2.67; OR for grade III-IV, 1.83) (68)

irAE, immune-related adverse events; OR, odds ratio; all are statistically significant (p<0.05); PPI, Proton-pump inhibitors; NSAID, nonsteroidal anti-inflammatory drugs; ACE, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; HR, hazards ratio; 1higher rate of irAE in vaccinated compared to unvaccinated (56% vs 26%); 2Pearson correlation coefficient R = 0.704; P < .001; 3compared to Non-small cell lung cancer/Renal Cell Carcinoma; 4 not necessarily irAE; 5 OR from two studies;*these are potential risk factors.