Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients

Figures & data

Figure 1 The flow diagram of literature search and selection.

Abbreviation: RCT, randomized controlled trial.

Table 1 Characteristics of studies including nivolumab-plus-ipilimumab and nivolumab therapy

Characteristics	Wolchok et al^Citation28 (2017)	Hassel et al^Citation29 (2017)	Hellman et al^Citation27 (2018)	Antonia et al^Citation26 (2016)
Designation	Check Mate 067	Check Mate-037, -066 and -067	Check Mate 227	Check Mate 032
Histology	Melanoma	Melanoma	NSCLC	SCLC
Design	Phase III RCT	Phase III RCT	Phase III RCT	Phase I/II trial, open-label
Patients (N/N+I)	313/313	787/407	391/576	98/61
Monotherapy	Nivolumab	Nivolumab	Nivolumab	Nivolumab
	3 mg/kg q2w	3 mg/kg q2w	3 mg/kg q2w	3 mg/kg q2w
Combine therapy	Nivolumab (1 mg/kg q2w)	Nivolumab (1 mg/kg q2w)	Nivolumab (3 mg/kg q2w)	Nivolumab (1 mg/kg q2w)
	plus ipilimumab (3 mg/kg q6w)	plus ipilimumab (3 mg/kg q6w)	plus ipilimumab (1 mg/kg q6w)	plus ipilimumab (3 mg/kg q6w)
Jaded score	5	5	5	3

Abbreviations: NSCLC, non-small-cell lung cancer; RCT, randomized controlled trial; SCLC, small-cell lung cancer; q2w, every 2 weeks; q6w, every 6 weeks.

Table 2 Incidence and OR of irAEs, including 95% CI and number of trials in each analysis

All-grade irAEs	No. of trials	Pooled OR (95% CI)	Pooled OR	P-value	High-grade irAEs	No. of trials	Pooled OR (95% CI)	Pooled OR	P-value
Pruritus	4	(1.739, 2.546)	2.104	P<0.05	Pruritus	4	(2.220, 25.919)	7.585	P<0.05
Rash	4	(1.488, 2.814)	2.046	P<0.05	Rash	4	(2.443, 10.061)	4.957	P<0.05
Vitiligo	2	(0.637, 1.264)	0.897	P<0.05	Vitiligo	2	(0.048, 4.410)	0.458	P<0.05
Diarrhea	4	(1.759, 4.192)	2.715	P<0.05	Diarrhea	4	(2.943, 7.628)	4.738	P<0.05
Colitis	3	(5.833,16.833)	9.909	P<0.05	Colitis	3	(6.148, 26.118)	12.671	P<0.05
ALT elevation	3	(3.732, 7.589)	5.322	P<0.05	ALT elevation	3	(3.819, 12.344)	6.866	P<0.05
AST elevation	3	(3.251, 6.656)	4.652	P<0.05	AST elevation	3	(0.376, 18.554)	2.643	P<0.05
Hypothyroidism	4	(1.413, 2.353)	1.823	P<0.05	Hypothyroidism	4	(0.674, 12.251)	2.874	P<0.05
Hyperthyroidism	3	(1.986, 4.374)	2.947	P<0.05	Hyperthyroidism	2	(1.036, 39.008)	6.356	P<0.05
Hypophysitis	2	(7.360, 46.437)	18.487	P<0.05	Hypophysitis	2	(1.696, 21.973)	6.105	P<0.05
Pneumonitis	3	(2.286, 6.399)	3.825	P<0.05	Pneumonitis	3	(1.206, 16.379)	4.445	P<0.05

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; irAEs, immune-related adverse events; OR, odds ratio.

Figure 2 Meta-analysis of the risk of pruritus.

Notes: (A) Forest plot of the risk of all-grade pruritus. (B) Forest plot of the risk of high-grade pruritus.

Figure 3 Meta-analysis of the risk of rash.

Notes: (A) Forest plot of the risk of all-grade rash. (B) Forest plot of the risk of high-grade rash. Weights are from random-effects analysis.

Figure 4 Meta-analysis of the risk of diarrhea.

Notes: (A) Forest plot of the risk of all-grade diarrhea. (B) Forest plot of the risk of high-grade diarrhea. Weights are from random-effects analysis.

Figure 5 Meta-analysis of the risk of colitis.

Notes: (A) Forest plot of the risk of all-grade colitis. (B) Forest plot of the risk of high-grade colitis.

Figure 6 Meta-analysis of the risk of ALT elevation.

Notes: (A) Forest plot of the risk of all-grade ALT elevation. (B) Forest plot of the risk of high-grade ALT elevation.
Abbreviation: ALT, alanine aminotransferase.

Figure 7 Meta-analysis of the risk of pneumonitis.

Notes: (A) Forest plot of the risk of all-grade pneumonitis. (B) Forest plot of the risk of high-grade pneumonitis.

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