Table 1.

CRS reported in recent clinical trials

Author/Year	Maude et al., 2018 [87]00	Park et al., 2018 [88] 00	Neelapu et al., 2017 [44] 00	Schuster et al., 2017 [89] 00	Turle et al., 2017	Gardner et al., 2017 [80] 8]	Ali et al., 2016 [79] 7]	Garfall et al., 2015 [90] 3]	Lee et al., 2015 [39] 5]	Maude et al., 2015 [32] 8]	Davila et al., 2014 [33] 9]	Kantarjian et al., 2017 [27] 4]	Stackelberg et al., 2016 [91] 5]	Topp et al., 2015 [68] 7]	Topp et al., 2014 [92] 6]
Institution	25 centers	MSKCC	22 centers	UPenn	FHCRC	SCHRI	NCI	UPenn	NCI	UPenn/UPhil	MSKCC	101 centers	26 centers	37 centers	9 centers
Applied therapy	CD19 CAR (4-1BB)	CD19 CAR (CD28)	CD19 CAR (CD28)	CD19 CAR (4-1BB)	CD19 CAR (4-1BB)	CD19 CAR (4-1BB)	BCMA CAR (CD28)	CD19 CAR (4-1BB)	CD19 CAR (CD28)	CD19 CAR (4-1BB)	CD19 CAR (CD28)	blinatumomab	blinatumomab	blinatumomab	blinatumomab
Disease	B-ALL	B-ALL	DLBCL/TFL/ PMBCL	DLBCL/TFL	CLL	B-ALL	MM	MM	B-ALL	B-ALL	B-ALL	B-ALL	B-ALL	B-ALL	B-ALL
Number of patients	75	53	101	28	24	45	12	11	20	30	16	267	70	189	36
Incidences
% CRS	77	85	93	57	83	93	501	18	66	100	NR	14,2	11	NR	NR
% sCRS (>°II)	46	26	13	18	8	23	171	9	32	27	44	4,9	5	3	0,8
% sNeurotox (>°II)	13	42	28	11	25	21	0	NR	1	3	13	9,4	4	11	14
treatment related deaths	12	13	34	15	16	0	0	0	0	0	0	37	68	19	310
sCRS correlates
tumor burden	NR	y*	NR	NR	y	n	NR	NR	y	y	y	NR	NR	NR	y
CRP/ferritin	n/y	NR	NR	NR	y*/y*	NR	NR	NR	y*/y*	y*11/y*	y*/NR	NR	NR	NR	NR
IL-6/IFNg	y/y	NR	y/n	NR	y*/y*	y/NR	NR	NR	y*/y*	y*/y*	n*/n*	NR	NR	NR	NR
Therapy
tocilizumab response	NR	NR	NR	1/1	5/6	NR	100	NR	50%12	100%	y	NR	NR	NR	NR
steroid response	NR	NR	NR	0/0	5/6	NR	NR	NR	y	y	y	NR	NR	NR	NR
Prognosis
CRS related to ORR?	NR	NR	NR	NR	NR	NR	NR	NR	y	NR	NR	NR	NR	2/3 CR	y
tocilizumab related to reduced ORR?	NR	NR	n	n	NR	n	n	NR	n	possible13	n	NR	NR	NR	NR
steroids related to reduced ORR?	NR	NR	n	NR	NR	n	NR	NR	n	possible13	y	NR	NR	NR	NR
Response
% ORR	81	83	82	64	71	100	25	NR	33	10	NR	NR	45	52	75
% CR (MRD -)	81 (81)	83 (6714)	55	57	17	93 (93)	8	NR	66 (62)	90	88 (75)	44	39 (20)	43 (32)	69 (61)

¹: no definition of CRS supplied, but patients showed signs of CRS. ²: death due to cerebral hemorrhage in the context of coagulopathy and resolving cytokine release syndrome. ³: 1 death due to °V CRS before dose adjustment to disease burden. ⁴: 2 deaths attributed to CRS, 1 to pulmonary embolism. ⁵: 1 death due to neurotoxicity. ⁶:1 death to °V CRS with °V cerebral edema refractory to tocilizumab, siltuximab, dexamethasone before reduction of CAR T cell dose. ⁷: not further specified. ⁸: 6 fatal AEs attributed to blinatumomab, one due to °IV CRS with °V respiratory failure. ⁹: 1 death due to fungal infection of the brain after HSCT classified as possibly related to blinatumomab. ¹⁰: 3 deaths due to sepsis and candida infection classified as possibly related to blinatumomab. ¹¹: CRP > 20 mg/dl: positive predictive value only 50%.¹²: 2 patients received steroids additional to tocilizumab for not reported reasons.¹³: 2 of 9 patients treated with immunosuppression (not further specified if related to tocilizumab or glucocorticoids) relapsed. ¹⁴: 48 patients evaluable. *: statistically significant

B-ALL acute lymphoblastic B cell leukemia, CLL chronic lymphocytic leukemia, DLBCL diffuse large B cell lymphoma, MM Multiple myeloma, MPM malignant pleural mesotheliomas, NR not reported, PDA pancreatic ductal adenocarcinoma, PMBCL primary mediastinal large B-cell lymphoma, TFL transformed follicular lymphoma, sNeurotox severe neurotoxicity