Occurrence of irAEs after Immune Checkpoint Inhibitor Rechallenge: An Updated Meta-Analysis

Table 1

Characteristics of the included studies.

Author (year)	Type of study	Disease	N◦ pts	Initial ICI type			Initial irAEs				Rechallenge ratios	Type of rechallenged ICIs			Rechallenged irAEs				Disease response after rechallenge		Quality (NOS score)
				PD-1 (PD-L1)	CTLA-4	Combo	Type	Total irAEs	Low-grade irAEs	High-grade irAEs		PD-1 (PD-L1)	CTLA-4	Combo	Type	Total irAEs	Low-grade irAEs	High-grade irAEs	ORR (%)	DCR
Abu-Sbeih et al. (2019) [14]	Retrospective	Various	NA	79	47	41	Diarrhea and/or colitis	167	105	62	167/167	135	32	0	Diarrhea and/or colitis	57	51	6	—	—	6
Abu-Sbeih et al. (2019) [26]	Retrospective	Various	2279	1434	627	218	Pancreatic injury	82	41	41	35/82	NA	NA	NA	Pancreatic injury	4	NA	NA	—	—	6
Abou Alaiwi et al. (2020) [27]	Retrospective	mRCC	499	NA	NA	NA	Global	80	37	43	36/80	32	0	4	Global	18	11	7	44	—	8
Albandar et al. (2021) [28]	Retrospective	Various	264	224	19	21	Global	133	70	45	39/133	NA	NA	NA	Global	36	19	17	41	24/39	6
Amode et al. (2017) [29]	Observational	Melanoma	82	0	82	0	NA	23	13	10	23/23	23	0	0	Global	14	10	4	21.7	8/23	7
Cortazar et al. (2020) [30]	Retrospective	Various	414	400	92	74	Acute kidney injury	138	NA	NA	31/138	NA	NA	NA	Acute kidney injury	7	NA	NA	—	—	7
Delyon et al. (2019) [31]	Prospective cohort	Melanoma	NA	NA	NA	NA	Diarrhea and/or colitis	25	NA	NA	11/25	8	2	1	Diarrhea and/or colitis	1	0	1	—	—	8
Dubey et al. (2020) [32]	Retrospective	Various	1834	1215	186	433	Neurological	NA	NA	28	10/28	NA	NA	NA	Neurological	6	NA	NA	—	—	6
Fujisaki et al. (2021) [33]	Retrospective	NSCLC	231	231	0	0	Global	93	68	25	14/93	14	0	0	Global	4	3	1	—	—	8
Fujita et al. (2019) [23]	Retrospective	NSCLC	18	18	0	0	Global	NA	NA	NA	18/18	18	0	0	Global	NA	NA	NA	0	7/18	5
Gutzmer et al. (2017) [34]	Retrospective	Melanoma	41	0	41	0	Global	22	10	12	22/22	22	0	0	NA	6	NA	NA	45.4	16/22	6
Kartolo et al. (2021) [35]	Retrospective	Various	NA	65	6	8	Global	85	64	21	40/85	NA	NA	NA	Global	31	NA	NA	—	—	5
Koyauchi et al. (2020) [36]	Retrospective	NSCLC	592	592	0	0	Pneumonitis	79	49	30	16/79	16	0	0	Pneumonitis	5	5	0	50	14/16	8
Li et al. (2020) [37]	Retrospective	Melanoma	1913	NA	NA	NA	Hepatitis	NA	NA	102	31/102	29	2	0	Hepatitis (4) others (11)	15	12	3	64.5	23/31	8
Miller et al. (2019) [38]	Retrospective	Various	5762	4001	1446	315	Hepatotoxicity	433	333	100	31/433	25	5	1	Hepatotoxicity	8	NA	NA	—	—	6
Morse et al. (2019) [39]	Retrospective	mCRC	119	0	0	119	Global	67	38	29	25/67	0	0	25	Global	14	8	6	—	—	7
Mouri et al. (2019) [40]	Retrospective	NSCLC	187	187	0	0	Global	49	34	15	21/49	21	0	0	Global	15	14	1	15	18/21	5
Naidoo et al. (2016) [41]	Retrospective	Various	915	716	0	199	Pneumonitis	43	31	12	12/43	NA	NA	NA	Pneumonitis	3	3	0	—	—	6
Pollack et al. (2017) [22]	Retrospective	Melanoma	NA	0	0	80	Global	80	25	55	80/80	80	0	0	Global	40	26	14	70	71/80	7
Santini et al. (2018) [18]	Retrospective	NSCLC	482	432	0	50	Global	68	35	33	38/68	38	0	0	Global	20	12	8	47.4	31/38	6
Siddiqui et al. (2021) [42]	Retrospective	GU cancers	2036	NA	NA	NA	Global	388	NA	NA	61/388	27	10	24	Global	46	32	14	36.1	46/61	6
Simonaggio et al. (2019) [43]	Cohort study	Various	159	NA	NA	NA	Global	96	46	50	40/96	35	0	4	Global	22	8	14	32.5	28/40	7
Weill et al. (2021) [44]	Retrospective	Various	NA	18	0	2	Myositis	20	NA	NA	9/20	8	1	0	Colitis	1	0	1	66.7	7/9	6
Williams et al. (2017) [45]	Retrospective	Various	NA	59	28	16	Global	103	78	25	86/103	NA	NA	NA	NA	86	73	13	—	—	6

CTLA-4, cytotoxic T-lymphocyte antigen-4; DCR, disease control rate; ICIs, immune checkpoint inhibitors; irAEs, immune-related adverse events; mCRC, metastatic colorectal cancer; mRCC, metastatic renal cell carcinoma; NA, not applicable; NSCLC, non-small-cell lung cancer; ORR, objective response rate; PD-1, programmed cell death protein-1; PD-L1, programmed cell death protein ligand-1.