Table 1. Univariable and multivariable... | American Society of Hematology

Table 1.

Univariable and multivariable analysis of baseline and therapy-related characteristics by severity of CRS

Characteristic	CRS grade
	0					1-3					4-5					Total
	No.	%	Median	IQR	Range	No.	%	Median	IQR	Range	No.	%	Median	IQR	Range	No.	%	Median	IQR	Range	Univariable P*	Multivariable P†
No. of patients	40					83					10					133
Age, years			56	44-65	27-70			54	43-61	20-73			53.5	43-62	20-70			54	43-62	20-73	.55	—
Sex																					.79	—
Male	28	30				59	63				6	7				93	70
Female	12	30				24	60				4	10				40	30
Karnofsky performance score																					.30	—
60-70	2	14				10	71				2	14				14	10
80-90	32	30				67	63				7	7				106	80
100	6	46				6	46				1	8				13	10
Disease type																					.30	—
ALL	12	25				31	66				4	9				47	35
CLL	4	17				18	75				2	8				24	18
NHL	24	39				34	55				4	6				62	47
Prior lines of therapy			3	2-5	1-11			4	3-5	1-11			5	3-7	2-9			4	3-5	1-11	.13	—
Prior transplant																					.38‡	—
Allogeneic only	3	12				21	84				1	4				25	19
Autologous only	9	41				11	50				2	9				22	17
Both	0	0				3	100				0	0				3	2
Marrow disease burden by flow cytometry (%)			0	0-1.3	0-79			20	0-65	0-97			21	3.6-40	0-89.8			1.3	0-42	0-97	<.0001	<.0001
Not involved	23	47				25	51				1	2				49	37
CD19⁺ cells in marrow by flow cytometry			3.6	1.3-6.6	0-79			22	3.0-66	0-99			22	11-40	0.3-90			8.8	2.2-48	0-99	.0001§	-
Platelet count (1000/μL)			98	58-159	11-265			69	38-119	1-553			32	19-85	5-162			77	40-133	1-553	.002	.05
CD8⁺ selection method																					.001	.03
Bulk CD8⁺	9	15				47	77				5	8				61	46
Central memory enriched	31	43				36	50				5	7				72	54
Lymphodepletion																					.67	.02
Cyclophosphamide/fludarabine based	30	29				65	62				9	9				104	78
Not cyclophosphamide/fludarabine based	10	35				18	62				1	3				29	22
CAR T-cell dose																					.002	.003
2 × 10⁵ EGFRt⁺ cells per kg	10	29				25	71				0	0				35	26
2 × 10⁶ EGFRt⁺ cells per kg	27	31				54	63				5	6				86	65
2 × 10⁷ EGFRt⁺ cells per kg	3	25				4	33				5	42				12	9
Lymphodepletion/CAR T-cell dose interaction effect\|\|																					.03	.009

Characteristic	CRS grade
	0					1-3					4-5					Total
	No.	%	Median	IQR	Range	No.	%	Median	IQR	Range	No.	%	Median	IQR	Range	No.	%	Median	IQR	Range	Univariable P*	Multivariable P†
No. of patients	40					83					10					133
Age, years			56	44-65	27-70			54	43-61	20-73			53.5	43-62	20-70			54	43-62	20-73	.55	—
Sex																					.79	—
Male	28	30				59	63				6	7				93	70
Female	12	30				24	60				4	10				40	30
Karnofsky performance score																					.30	—
60-70	2	14				10	71				2	14				14	10
80-90	32	30				67	63				7	7				106	80
100	6	46				6	46				1	8				13	10
Disease type																					.30	—
ALL	12	25				31	66				4	9				47	35
CLL	4	17				18	75				2	8				24	18
NHL	24	39				34	55				4	6				62	47
Prior lines of therapy			3	2-5	1-11			4	3-5	1-11			5	3-7	2-9			4	3-5	1-11	.13	—
Prior transplant																					.38‡	—
Allogeneic only	3	12				21	84				1	4				25	19
Autologous only	9	41				11	50				2	9				22	17
Both	0	0				3	100				0	0				3	2
Marrow disease burden by flow cytometry (%)			0	0-1.3	0-79			20	0-65	0-97			21	3.6-40	0-89.8			1.3	0-42	0-97	<.0001	<.0001
Not involved	23	47				25	51				1	2				49	37
CD19⁺ cells in marrow by flow cytometry			3.6	1.3-6.6	0-79			22	3.0-66	0-99			22	11-40	0.3-90			8.8	2.2-48	0-99	.0001§	-
Platelet count (1000/μL)			98	58-159	11-265			69	38-119	1-553			32	19-85	5-162			77	40-133	1-553	.002	.05
CD8⁺ selection method																					.001	.03
Bulk CD8⁺	9	15				47	77				5	8				61	46
Central memory enriched	31	43				36	50				5	7				72	54
Lymphodepletion																					.67	.02
Cyclophosphamide/fludarabine based	30	29				65	62				9	9				104	78
Not cyclophosphamide/fludarabine based	10	35				18	62				1	3				29	22
CAR T-cell dose																					.002	.003
2 × 10⁵ EGFRt⁺ cells per kg	10	29				25	71				0	0				35	26
2 × 10⁶ EGFRt⁺ cells per kg	27	31				54	63				5	6				86	65
2 × 10⁷ EGFRt⁺ cells per kg	3	25				4	33				5	42				12	9
Lymphodepletion/CAR T-cell dose interaction effect\|\|																					.03	.009

IQR, interquartile range.

Two-sided P values were calculated by using the Kruskal-Wallis test for continuous variables and Fisher’s exact test for categorical variables.

†

Step-wise multivariable proportional odds models were performed to assess the impact of baseline factors on the occurrence of CRS (grade 0 vs 1-3 vs 4-5), where log₁₀ values were used to transform data as appropriate, with 0.001 substituting for values of 0.

‡

Any transplant type vs no transplant.

Because marrow disease burden and total CD19⁺ cells in marrow have a strong correlation (r = 0.99; P < .0001), only marrow disease was included in the multivariable analysis.

The interaction effect demonstrates that at increasing CAR T-cell dose levels, the incorporation of fludarabine into the lymphodepleting regimen has a greater association with CRS.

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