Real-world healthcare resource utilization and costs associated with tisagenlecleucel and axicabtagene ciloleucel among patients with diffuse large B-cell lymphoma: an analysis of hospital data in the United States

Figures & data

Figure 1. Sample selection flowchart. axi-cel: axicabtagene ciloleucel; CAR-T: chimeric antigen receptor modified T-cells; DLBCL: diffuse large B-cell lymphoma; Q: quarter; tisa-cel: tisagenlecleucel.

Table 1. Patient baseline characteristics.

	Tisa-cel (N = 33)	Axi-cel (N = 86)	p
Demographics
Age (years)
Mean ± SD	62.3 ± 11.7	59.8 ± 12.2	.31
Median (range)	65.0 (23.0, 79.0)	60.5 (26.0, 84.0)	–
Sex, n (%)			.19
Male	18 (54.6%)	58 (67.4%)
Female	15 (45.5%)	28 (32.6%)
Race and ethnicity, n (%)			.16
White	25 (75.8%)	54 (62.8%)
Black	1 (3.0%)	6 (7.0%)
Hispanic	5 (15.2%)	8 (9.3%)
Other/unknown	2 (6.1%)	18 (20.9%)
Year of index date, n (%)			.49
2018	7 (21.2%)	24 (27.9%)
2019	22 (66.6%)	48 (55.8%)
2020 Q1	4 (12.1%)	14 (16.3%)
Attending physician specialty, n (%)			.86
Hematology/oncology	26 (78.8%)	69 (80.2%)
Unknown	7 (21.2%)	17 (19.8%)
Primary payer, n (%)			.18
CMS Medicare and Medicaid	23 (69.7%)	42 (48.8%)
Commercial	8 (24.2%)	29 (33.7%)
Managed care	1 (3.0%)	10 (11.6%)
Other	1 (3.0%)	5 (5.8%)
Comorbidities, n (%)
Hypertension	19 (57.6%)	39 (45.4%)	.23
Depression	12 (36.4%)	16 (18.6%)	.04*
Diabetes	10 (30.3%)	18 (20.9%)	.28
Renal disease	7 (21.2%)	7 (8.1%)	.06
Chronic pulmonary disease	3 (9.1%)	13 (15.1%)	.55
Cerebrovascular disease	1 (3.0%)	3 (3.5%)	>.99
NCI Comorbidity Index, mean ± SD	1.6 ± 1.8	1.4 ± 1.8	.55
NCI comorbidities, n (%)
Diabetes	10 (30.3%)	18 (20.9%)	.28
Renal disease	7 (21.2%)	7 (8.1%)	.06
Chronic obstructive pulmonary disease	3 (9.1%)	15 (17.4%)	.39
Peripheral vascular disease	4 (12.1%)	7 (8.1%)	.50
Congestive heart failure	3 (9.1%)	9 (10.5%)	>.99
History of myocardial infarction	1 (3.0%)	6 (7.0%)	.67
Dementia	2 (6.1%)	3 (3.5%)	.62
Mild liver disease	0 (0.0%)	4 (4.7%)	.57
Cerebrovascular disease	1 (3.0%)	3 (3.5%)	>.99
Rheumatologic disease	2 (6.1%)	0 (0.0%)	.08
Moderate or severe liver disease	1 (3.0%)	1 (1.2%)	.48
Acute myocardial infarction	0 (0.0%)	1 (1.2%)	>.99
Peptic ulcer disease	1 (3.0%)	0 (0.0%)	.28
Paralysis (hemiplegia or paraplegia)	0 (0.0%)	1 (1.2%)	>.99
AIDS	0 (0.0%)	1 (1.2%)	>.99

AIDS: acquired immunodeficiency syndrome; axi-cel: axicabtagene ciloleucel; CMS: Centers for Medicare & Medicaid Services; NCI: National Cancer Institute; Q, quarter; SD: standard deviation; tisa-cel: tisagenlecleucel.

*p< .05.

Table 2. Infusion center characteristics.

	Center type
	All centers^a (N = 15)	Tisa-cel centers (N = 7)	Axi-cel centers (N = 11)
Provider US census region, n (%)
Northeast	3 (20.0%)	0 (0.0%)	3 (27.3%)
Midwest	4 (26.7%)	3 (42.9%)	3 (27.3%)
South	6 (40.0%)	3 (42.9%)	4 (36.4%)
West	2 (13.3%)	1 (14.3%)	1 (9.1%)
Vicinity of provider to a city center, n (%)
Urban	15 (100.0%)	7 (100.0%)	11 (100.0%)
Rural	0 (0.0%)	0 (0.0%)	0 (0.0%)
Teaching or non-teaching hospital, n (%)
Teaching	13 (86.7%)	7 (100.0%)	9 (81.8%)
Non-teaching	2 (13.3%)	0 (0.0%)	2 (18.2%)
Number of beds, n (%)
100–199	1 (6.7%)	0 (0.0%)	1 (9.1%)
200–299	1 (6.7%)	1 (14.3%)	1 (9.1%)
300–399	1 (6.7%)	0 (0.0%)	1 (9.1%)
400–499	1 (6.7%)	1 (14.3%)	0 (0.0%)
≥500	11 (73.3%)	5 (71.4%)	8 (72.7%)

axi-cel: axicabtagene ciloleucel; tisa-cel: tisagenlecleucel; US: United States.

a Three centers were eligible to administers both types of infusions.

Table 3. HRU associated with tisa-cel and axi-cel.

	Tisa-cel (N = 33)	Axi-cel (N = 86)	Tisa-cel vs. Axi-cel
			Unadjusted IRR (95% CI)	p
Resource use during the infusion encounter (per patient)
IP admission for infusion
Number of patients, n (%)	25 (75.8%)	86 (100.0%)	–	<.01*
Length of stay^a
Mean ± SD	11.30 ± 8.47	18.33 ± 9.90	–	<.01*
Median [1st quartile, 3rd quartile]	13.0 [5.0, 14.0]	15.5 [12.0, 21.0]
Readmission
Patients with readmission in 30 days, n (%)^b	4 (16.0%)	16 (18.6%)	–	>.99
Patients with readmission in 60 days, n (%)^b	6 (24.0%)	21 (24.4%)	–	.97
ICU
Number of patients, n (%)	3 (9.1%)	18 (20.9%)	–	.13
ICU days
Among all patients, mean ± SD	0.48 ± 1.79	1.67 ± 5.33	–	.14
Among patients with ICU stay, mean ± SD	5.33 ± 3.51	8.00 ± 9.41	–	.92
OP visit for infusion
Number of patients, n (%)	8 (24.2%)	0 (0.0%)	–	–
Resource use during the entire follow-up period (PPPM)
Length of follow-up in months, mean ± SD	4.95 ± 4.35	3.31 ± 3.44	–	.11
IP admission
Number of patients, n (%)	30 (90.9%)	86 (100.0%)	–	.02*
Number of IP admissions	0.33	0.46	0.72 (0.47, 1.09)	.12
Length of stay^a	3.86	6.85	0.56 (0.33, 0.96)	.03*
ICU
Number of patients, n (%)	7 (21.2%)	26 (30.2%)	–	.33
Number of ICU stays	0.04	0.09	0.45 (0.16, 1.29)	.14
ICU days	0.42	0.82	0.51 (0.13, 2.04)	.34
OP visit
Number of patients, n (%)	27 (81.8%)	45 (52.3%)	–	<.01*
Number of OP visits	2.17	1.17	1.86 (1.13, 3.05)	.01*

axi-cel: axicabtagene ciloleucel; CAR-T: chimeric antigen receptor modified T-cells; CI: confidence interval; HRU: healthcare resource utilization; ICU: intensive care unit; IP: inpatient; IRR: incidence rate ratio; OP: outpatient; PPPM: per-patient-per-month; SD: standard deviation; tisa-cel: tisagenlecleucel.

*p< .05.

a Inpatient length of stay includes ICU days.

b Percentages are calculated among patients who received CAR-T infusion in the inpatient setting.

Figure 2. Healthcare costs in the tisa-cel and axi-cel cohorts. During both the infusion encounter and over the entire follow-up period, tisa-cel was associated with significantly lower overall costs and inpatient costs compared with axi-cel (all comparisons p< .05). axi-cel: axicabtagene ciloleucel; IP: inpatient; OP: outpatient; PPPM: per-patient-per-month; tisa-cel: tisagenlecleucel.

Table 4. AEs and related treatments in the tisa-cel and axi-cel cohorts.

	Tisa-cel (N = 33)	Axi-cel (N = 86)	Tisa-cel vs. Axi-cel
			p
CRS^a
Any patients with grade ≥3 CRS, n (%)	2 (6.1%)	13 (15.1%)	.23
Patients with grade 3 CRS, n (%)	0 (0.0%)	3 (3.5%)	.56
Patients with grade 4 CRS, n (%)	1 (3.0%)	6 (7.0%)	.67
Patients with grade 5 CRS, n (%)	1 (3.0%)	4 (4.7%)	>.99
Tocilizumab use among all patients with CAR-T infusion
Number of tocilizumab users, n (%)	5 (15.2%)	44 (51.2%)	<.01*
Number of days with tocilizumab use among users^b, mean ± SD	1.2 ± 0.5	1.8 ± 0.9	.18
Number of tocilizumab infusions among users^c, mean ± SD	1.2 ± 0.5	1.9 ± 1.1	.16
NT^d
Any NT, n (%)	7 (21.2%)	31 (36.0%)	.12
Encephalopathy, n (%)	5 (15.2%)	25 (29.1%)	.12
Aphasia, n (%)	1 (3.0%)	8 (9.3%)	.44
Mental status changes/disorientation, n (%)	0 (0.0%)	5 (5.8%)	.32
Delirium, n (%)	1 (3.0%)	2 (2.3%)	>.99
Cerebral edema, n (%)	1 (3.0%)	3 (3.5%)	>.99
Agitation/restlessness, n (%)	1 (3.0%)	0 (0.0%)	.28
Seizure, n (%)	0 (0.0%)	1 (1.2%)	>.99
Speech disorder, n (%)	0 (0.0%)	0 (0.0%)	>.99
Disturbance in attention, n (%)	0 (0.0%)	0 (0.0%)	>.99
Somnolence, n (%)	0 (0.0%)	0 (0.0%)	>.99
Abnormal motor activity, n (%)	0 (0.0%)	0 (0.0%)	>.99
Steroid use among patients with NT
Number of patients with NT, n	7	31
Number of steroid users, n (%)	5 (71.4%)	24 (77.4%)	>.99
Number of days with steroid use among users^b, mean ± SD	12.00 ± 9.95	12.50 ± 10.12	.93
Number of times steroids used among users^c, mean ± SD	13.80 ± 10.43	16.83 ± 19.07	>.99
Hypogammaglobulinemia^e
Any hypogammaglobulinemia, n (%)	10 (30.3%)	17 (19.8%)	.22
Patients diagnosed based on ICD-10 CM code, n (%)	8 (24.2%)	10 (11.6%)	.09
Patients diagnosed based on IVIG use, n (%)	8 (24.2%)	15 (17.4%)	.40
IVIG use among patients with hypogammaglobulinemia
Number of IVIG users, n (%)	8 (80.0%)	15 (88.2%)	.61
Number of days with IVIG use among users^b, mean ± SD	3.00 ± 1.93	2.07 ± 1.79	.23
Number of IVIG infusions among users^c, mean ± SD	3.38 ± 1.85	2.80 ± 2.14	.40
Time from CAR-T infusion to first IVIG use among users
<1 month, n (%)	3 (37.5%)	3 (20.0%)	.62
1–2 months, n (%)	2 (25.0%)	2 (13.3%)	.59
>2 months, n (%)	3 (37.5%)	10 (66.7%)	.22

AE: adverse event; axi-cel: axicabtagene ciloleucel; CAR-T: chimeric antigen receptor modified T-cells; CRS: cytokine release syndrome; ICD-10 CM: International Classification of Diseases, 10th edition, Clinical Modification; ICU: intensive care unit; IVIG: intravenous immunoglobulin; NT: neurologic toxicity; SD: standard deviation; tisa-cel: tisagenlecleucel.

*p< .05.

a CRS events (grade ≥3) were identified using billing data that indicated ICU and vasopressor or ventilation support within one-month post-CAR-T infusion.

b Multiple billing data records indicating AE treatments on a single service day were counted once. However, the majority of the patients had one tocilizumab/steroid/IVIG use on one day.

c Assumed each billing data record indicates one medication use, with the caveat that multiple packages, although billed separately, were for single infusion/injection.

d Neurologic toxicity events were identified using ICD-10 CM codes, within one-month post-CAR-T infusion.

e Hypogammaglobulinemia events were identified using ICD-10 CM code or the use of IVIG.

Data availability statement

The data were provided to the authors under an agreement with Premier Healthcare Solution, Inc. Researchers can request access from Premier directly and pay the applicable fee (https://products.premierinc.com/applied-sciences/solutions).