Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor-related pneumonitis

Figures & data

Table 1 Incidence of pneumonitis in important clinical trials of checkpoint inhibitors in advanced malignancies

Study	Drug	Number of patients (%) with all-grade pneumonitis	Number of patients (%) with grade 3–4 pneumonitis
Melanoma
Ribas et al^Citation51	Pembrolizumab 2 mg/kg q3w	3 (2)	0 (0)
	Pembrolizumab 10 mg/kg q3w	3 (2)	2 (1)
Robert et al^Citation20	Pembrolizumab 10 mg/kg q2w	0 (0)	0 (0)
	Pembrolizumab 10 mg/kg q3w	0 (0)	0 (0)
	Ipilimumab 3 mg/kg q3w	0 (0)	0 (0)
Robert et al^Citation19	Pembrolizumab 2 mg/kg q3w	2 (2)	1 (1)
	Pembrolizumab 10 mg/kg q3w	1 (1)	0 (0)
Weber et al^Citation6	Nivolumab 3 mg/kg q2w	5 (2)	0 (0)
Robert et al^Citation16	Nivolumab 3 mg/kg q2w	3 (2)	0 (0)
Margolin et al^Citation29	Ipilimumab 10 mg/kg q3w	0 (0)	0 (0)
Hodi et al^Citation2	Ipilimumab 3 mg/kg q3w	0 (0)	0 (0)
Wolchok et al^Citation28	Ipilimumab 0.3 mg/kg q3w	0 (0)	0 (0)
	Ipilimumab 3 mg/kg q3w	0 (0)	0 (0)
	Ipilimumab 10 mg/kg q3w	0 (0)	1 (1)
NSCLC
Borghaei et al^Citation17	Nivolumab 3 mg/kg q2w	4 (1)	3 (1)
Brahmer et al^Citation3	Nivolumab 3 mg/kg q2w	2 (2)	1 (1)
Herbst et al^Citation30	Pembrolizumab 2 mg/kg q3w	14 (4)	6 (2)
	Pembrolizumab 10 mg/kg q3w	12 (4)	6 (2)
Rizvi et al^Citation15	Nivolumab 3 mg/kg q2w	6 (5)	4 (3)
Gettinger et al^Citation10	Nivolumab 1 mg/kg q2w	3 (9)	2 (6)
	Nivolumab 3 mg/kg q2w	1 (3)	0 (0)
	Nivolumab 10 mg/kg q2w	4 (7)	1 (2)
Garon et al^Citation11	Pembrolizumab 2 mg/kg q3w	0 (0)	Reported as 9 (2%) patients total, among all groups
	Pembrolizumab 10 mg/kg q3w	13 (5)
	Pembrolizumab 2 mg/kg q2w	5 (3)
RCC
Motzer et al^Citation5	Nivolumab 3 mg/kg q2w	Not reported	Not reported
Bladder cancer
Rosenberg et al^Citation7	Atezolizumab 1200 mg q3w	7 (2)	2 (1)

Abbreviations: NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma; q3w, every 3 weeks; q2w, every 2 weeks.

Table 2 Management of pneumonitis by grade

Grade of pneumonitis	Symptoms	Management
Grade 1	None	Delay treatment
	Radiographic changes only	Repeat imaging every 3 weeks
Grade 2	Mild to moderate	Delay treatment
	Dyspnea and cough	Consider admission to hospital
		Methylprednisolone IV 0.5–1.0 mg/kg/day
		Taper steroids over 1 month
		Repeat imaging in days to weeks
Grade 3–4	Severe	Delay treatment, consider permanent cessation
	Hypoxia	Admit to hospital or ICU
	Life-threatening respiratory compromise	Methylprednisolone IV 2–4 mg/kg/day
		Consider additional immunosuppression at 48 hours
		Taper steroids over 6 weeks
		Repeat imaging in days to weeks

Abbreviations: IV, intravenous; ICU, intensive care unit.

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