Immunoglobulin somatic hypermutation has clinical impact in DLBCL and potential implications for immune checkpoint blockade and neoantigen-based immunotherapies

Xu-Monette, Zijun Y.; Li, Jianyong; Xia, Yi; Crossley, Beryl; Bremel, Robert D.; Miao, Yi; Xiao, Min; Snyder, Thomas; Manyam, Ganiraju C.; Tan, Xiaohong; Zhang, Hongwei; Visco, Carlo; Tzankov, Alexandar; Dybkaer, Karen; Bhagat, Govind; Tam, Wayne; You, Hua; Hsi, Eric D.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J. M.; Møller, Michael B.; Piris, Miguel A.; Winter, Jane N.; Medeiros, Jeffrey T.; Xu, Bing; Li, Yong; Kirsch, Ilan; Young, Ken H.

doi:10.1186/s40425-019-0730-x

Table 1 Clinicopathologic and molecular characteristics of patients with DLBCL with a low or high degree of SHM in immunoglobulin variable region genes

From: Immunoglobulin somatic hypermutation has clinical impact in DLBCL and potential implications for immune checkpoint blockade and neoantigen-based immunotherapies

	IGHV SHM^low	IGHV SHM^high	P	IGK/LV SHM^low	IGK/LV SHM^high	P
	n (%)	n (%)	P	n (%)	n (%)	P
Age
< 60 years	32 (44%)	25 (36%)	.31	66 (40%)	14 (37%)	.72
≥ 60 years	40 (56%)	45 (64%)		97 (60%)	24 (63%)
Sex
Male	35 (49%)	41 (59%)	.24	94 (58%)	26 (68%)	.27
Female	37 (51%)	29 (41%)		69 (42%)	12 (32%)
Stage
I - II	29 (43%)	34 (52%)	.39	72 (46%)	14 (39%)	.58
III - IV	39 (57%)	32 (48%)		86 (54%)	22 (61%)
B symptoms
No	38 (56%)	43 (63%)	.48	103 (66%)	28 (78%)	.23
Yes	30 (44%)	25 (37%)		53 (34%)	8 (22%)
Serum LDH level
Normal	21 (33%)	29 (45%)	.20	67 (46%)	18 (55%)	.44
Elevated	43 (67%)	35 (55%)		78 (54%)	15 (45%)
No. of extranodal sites
0 or 1	51 (76%)	53 (82%)	.53	126 (81%)	26 (70%)	.18
≥ 2	16 (24%)	12 (18%)		30 (19%)	11 (30%)
ECOG performance status
0 or 1	47 (80%)	44 (76%)	.66	113 (79%)	26 (81%)	1.0
≥ 2	12 (20%)	14 (24%)		30 (21%)	6 (19%)
Largest tumor size
< 5 cm	37 (66%)	27 (53%)	.17	73 (57%)	13 (43%)	.22
≥ 5 cm	19 (34%)	24 (47%)		55 (43%)	17 (57%)
IPI score
0–2	40 (60%)	42 (64%)	.72	97 (62%)	21 (57%)	.58
3–5	27 (40%)	24 (36%)		60 (38%)	16 (43%)
Therapy response
CR	51 (71%)	54 (77%)	.45*	126 (77%)	27 (73%)	.67*
PR	10	8		21	3
SD	2	3		4	1
PD	9	5		12	6
ABC subtype/ABC subtype
GCB	27 (39%)	39 (53%)	.094	78 (47%)	21 (57%)	.36
ABC	43 (61%)	34 (47%)		88 (53%)	16 (43%)
BAGS classification
CC/CB	24 (52%)	40 (75%)	.02	77 (64%)	21 (81%)	.11
Others	22 (48%)	13 (25%)		43 (36%)	5 (19%)
BCL2 translocation
No	55 (87%)	46 (72%)	.047	125 (81%)	22 (65%)	.042
Yes	8 (13%)	18 (28%)		29 (19%)	12 (35%)
MYC expression
< 70%	39 (57%)	50 (72%)	.047	117 (72%)	26 (68%)	.69
≥ 70%	29 (43%)	19 (28%)		46 (28%)	12 (32%)
PI3K expression
< 70%	43 (67%)	50 (75%)	.44	112 (72%)	14 (42%)	.0018
≥ 70%	21 (33%)	17 (25%)		43 (28%)	19 (58%)
p63 expression
< 10%	47 (68%)	38 (54%)	.086	93 (59%)	14 (39%)	.04
≥ 10%	22 (32%)	33 (46%)		65 (41%)	22 (61%)
CD30 expression
< 20%	58 (83%)	60 (83%)	1.0	135 (82%)	37 (97%)	.012
≥ 20%	12 (17%)	12 (17%)		30 (18%)	1 (3%)
p65 expression
< 10%	22 (35%)	29 (43%)	.47	61 (41%)	7 (21%)	.031
≥ 10%	40 (65%)	39 (57%)		89 (59%)	27 (79%)
CXCR4 expression
< 20%	43 (73%)	47 (70%)	.84	109 (72%)	19 (53%)	.029
≥ 20%	16 (27%)	20 (30%)		42 (28%)	17 (47%)

Abbreviations: IGHV Immunoglobulin heavy chain variable region gene, IGK/LV Immunoglobulin kappa or lambda light chain variable region gene, SHM^low Low degree of somatic hypermutation, SHM^high High degree of somatic hypermutation, LDH Lactate dehydrogenase, ECOG Eastern Cooperative Oncology Group, IPI International Prognostic Index, CR Complete response, PR Partial response, SD Stable disease, PD Progressive disease, GCB germinal center B-cell–like, ABC Activated B-cell–like, BAGS B-cell–associated gene signature, CB Centroblast subtype, CC Centrocyte subtype
Note: Not all patients had data available. Significant P values (Fisher’s exact test) are in bold. *For therapy response, P values were for comparisons between CR and non-CR cases

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