Table 3.

Overview of observational studies regarding immune-related adverse events in elderly patients with cancer

Study (first author, year)	No. of patients	Tumour type	Checkpoint inhibitor	Relevant outcome	Results
Sattar, 2018 [44]	N = 78 26 (33%) aged 65–74 years, 23 (30%) aged ≥ 75 years	Melanoma NSCLC Renal cell carcinoma	Ipilimumab Nivolumab Pembrolizumab	irAEs	41 (53%) patients with irAEs, 12 (15%) multiple irAEs Any grade irAEs Age < 65 years (n = 29): 41% Age 65–74 years (n = 26): 58% Age ≥ 75 years (n = 23): 61% Grade ≥ 3 irAEs Age < 65 years (n = 17): 29% Age 65–74 years (n = 12): 25% Age ≥ 75 years (n = 11): 36%
Chiarion Sileni, 2014 [45]	N = 855, 193 patients aged > 70 years	Melanoma	Ipilimumab	irAEs	Any irAE: age > 70 years: 50%, age < 70 years 46% Grade 3–4 irAE: age > 70 years: 6%, age < 70 years: no data
Leroy, 2019 [46]	N = 52, 23 patients aged ≥ 80 years	Melanoma	Ipilimumab	irAEs Treatment irAEs Hospitalisation because of irAEs	Any irAE: age ≥ 80 years: 65%, age ≤ 80 years: 52% Grade ≥ 3 irAE: age ≥ 80 years: 22%, age ≤ 80 years: 19% Corticosteroid treatment: age ≥ 80 years: 22%, age ≤ 80 years: 19% Additive immunosuppressive therapy: age ≥ 80 years: 9%, age ≤ 80 years: 4% Hospitalisation: age ≥ 80 years: 22%, age ≤ 80 years: 9%
Freeman, 2015 [47]	N = 148, 52 (35%) aged ≥ 65 years	Melanoma	Nivolumab	irAEs	Most common irAEs: Rash: Age ≥ 65 years: 40.4%, age < 65 years: 38.5% Diarrhoea: age ≥ 65 years: 21.2%, age < 65 years: 30.2% Vitiligo: age ≥ 65 years: 7.7%, age < 65 years: 10.4%
Betof, 2017 [19]	N = 254, 65 (25.6%) aged 65–74 years, 47 (18.5%) aged ≥ 75 years	Melanoma	Anti-PD-1 Anti-PD-L1	irAEs	110 (43.3%) irAEs in all patients Age 65–74 years: more arthritis (10.8%, p = 0.02) Age ≥ 75 years trend to more endocrine toxicity
Wong, 2017 [48]	N = 91, 64% ECOG PS 0–1, 18% ECOG PS 2, 9% ECOG PS 3	Melanoma	Anti-PD-1	irAEs	Treatment-related AEs grade ≥ 3: ECOG PS 0–1: 5% ECOG PS 2: 13% ECOG PS: 30% irAEs grade ≥ 3: ECOG PS 0–1: 15% ECOG PS 2: 0% ECOG PS 3: 0%
Horvat, 2015 [49]	N = 298	Melanoma	Ipilimumab	Number of irAEs Treatment irAEs	254 (85%) irAE 56 (19%) treatment discontinuation 103 (35%) corticosteroid treatment 29 (10%) anti-TNFα treatment
Luciani, 2018 [50]	Patients aged ≥ 75 years N = 72	NSCLC	Nivolumab Pembrolizumab	irAEs	9 (14%) irAEs 4 (40%) grade 3–4 irAEs
Corral de la Fuente, 2019 [51]	N = 98 27 aged ≥ 70 years	NSCLC	Anti-PD-1 Anti-PD-L1	irAEs	30.6% irAEs No statistically significant differences between older and younger patients
Verzoni, 2019 [52]	N = 389 70 aged ≥ 75 years	Renal cell carcinoma	Nivolumab	drAEs irAEs Treatment discontinuation	32% any drAE 7% grade ≥ 3 drAE 20% any grade irAE 2% grade 3 irAE <1% grade 4 irAE 7.9% treatment discontinuation, of which 45% because of irAEs
Muchnik, 2019 [53]	Patients aged ≥ 70 years N = 75 53% CCI ≥ 3 49% ECOG PS ≥ 2	NSCLC	Nivolumab Pembrolizumab “Other”	irAEs Treatment irAEs Hospitalisation	37% of any grade irAE 8% grade ≥ 3 irAE 64 patients discontinued treatment, 15% because of irAEs 64% of patients with irAE glucocorticoid treatment 72% hospitalisation during treatment
Silva, 2018 [54]	Patients aged ≥ 65 years N = 106	Lung cancer Melanoma Urological cancer Colorectal cancer	Nivolumab Pembrolizumab Ipilimumab Atezolizumab	irAEs	21 irAEs 5 severe irAEs Frailty predicted risk to AE: OR 3.03 (95% CI 1.36–6.74; p = 0.006)

AE adverse event, CCI Charlson Comorbidity Index, CI confidence interval, drAE drug-related adverse event, ECOG PS ECOG performance status, irAEs immune-related adverse events, N number of included patients, NSCLC non-small cell lung cancer, OR odds ratio, PD-1 programmed cell death-1, PD-L1 programmed cell death-ligand 1, TNF tumour necrosis factor