A Case in Which HLA-DR4 is Involved in the Development of Complex Immune-Related Endocrinological Adverse Events following Combination Therapy with Nivolumab and Ipilimumab

Table 1

Reported cases.

Patient no	Age (years)	Gender	Country	Tumor type	Drug (ICIs)	T1DM time of onset	Thyroid disease’s time of onset	Hypophysitis time of onset	Addison’s disease time of onset	HLA type	Reference no
1	54	Male	USA	Melanoma	Nivolumab ipilimumab	20 weeks	2 weeks	20 weeks	—	A2, DQB106 : 02	[7]
2	78	Female	Italy	Melanoma	Pembrolizumab	4 weeks	10 weeks	—	10 weeks	DRB104 : 16, DQB102 : 05	[8]
3	60	Male	Italy	Lung adenocarcinoma	Atezolizumab	6 weeks	—	12 weeks	12 weeks	DRB104, DQB103	[9]
4	68	Female	Japan	Renal cell carcinoma	Nivolumab	13 weeks	2 weeks	—	—	DRB109 : 01, DQB103 : 03	[10]
5	66	Female	USA	Sarcomatoid SCC	PD-1 inhibitor	7 weeks	N/A	—	—	DR3-DQ2, DR4-DQ8	[11]
6	55	Female	USA	Melanoma	Nivolumab, ipilimumab	5 months	N/A	—	—	A2, DRB104	[12]
7	64	Female	USA	Melanoma	Pembrolizumab	<1 month	N/A	—	—	DRB104	[12]
8	68	Male	Korea	SCC	Pembrolizumab	7 weeks	N/A	—	—	DRB109 : 01, DQB103 : 03	[13]
9	48	Male	Japan	Parotid gland adenocarcinoma	Nivolumab	17 weeks	15 weeks	—	—	DRB104 : 05	[14]
10	61	Male	Belgium	NSCLC	Pembrolizumab	8 weeks	8 weeks	—	—	DRB104, DQA103 : 01, DQB103 : 02	[15]
11	82	Male	Australia	SCC	Pembrolizumab	9 weeks	N/A	—	—	DRB104, DQB103 : 02	[16]
12	23	Male	Australia	Melanoma	Pembrolizumab	8 weeks	N/A	—	—	DRB103,DRB104 DQB103 : 02	[16]
13	83	Male	Belgium	Melanoma	Pembrolizumab	N/A	N/A	—	—	DRB101 : 01, DQA101, DQB105 : 01/DRB116 : 01, DQA101, DQB105 : 02	[17]
14	65	Male	Belgium	Melanoma	Pembrolizumab	N/A	N/A	—	—	DRB104 : 01, DQA102, DQB102 : 02/DRB107 : 01, DQA103, DQB103 : 01	[17]
Present case	42	Female	Japan	Melanoma	Nivolumab, ipilimumab	10 weeks	7 weeks	16 weeks	—	DRB104 : 05, DQB104 : 01	—

ICIs, immune checkpoint inhibitors; NSCLC, non-small cell lung cancer; SCC, squamous cell carcinoma; T1DM, type 1 diabetes mellitus; N/A, not available.