Process, resource and success factors associated with chimeric antigen receptor T-cell therapy for multiple myeloma

Figures & data

Table 1. Mean years of experience by interviewee position and type of experience.

	Oncologists and direct care providers (n = 5)	CAR-T co-ordinators (n = 3)	Facility administrators (n = 4)
Oncology (years)	16.0	13.3	15.9
Clinical trials (years)	9.8	9.0	5.5
Clinical practice (years)	14.3	13.5	6.0
BMT (years)	14.3	19.7	10.9
CAR-T	6.3	6.0	4.1
CD19	6.3	4.0	3.8
BCMA	2.2	1.3	2.0
Patients treated with CAR-T (n)	34.6	61.7	33.1
Experience with outpatient CAR-T administration
Yes	6	3	4
No	0	0	0

BMT: Bone marrow transplant; CAR-T: Chimeric antigen receptor T-cell.

Figure 1. Current presumed process of care for chimeric antigen receptor T-cell therapy: process map.

CAR: Chimeric antigen receptor; CRS: Cytokine release syndrome; h: Hour; HGG: Hypogammaglobulinemia; MAS: Macrophage activation syndrome.

Table 2. Current presumed standard-of-care process map summary^†.

Component (step)	Time (h): mean (min, max)	Personnel (USD$): mean (min, max)	Equipment (USD$): mean (min, max)	Physical plant (USD$): mean (min, max)	Total costs (USD$): mean (min, max)
Totals	472.9 (262.8, 683.1)	37,045 (17,779, 56,310)	6890 (6487, 7293)	1191 (597, 1785)	45,126 (24,863, 65,389)
Screening (steps 1–4)	41.5 (30.5, 52.4)	9199 (5793, 12,605)	3106 (3095, 3116)	172 (134, 210)	12,477 (9022, 15,932)
1. Pre-screening	4.3 (2.7, 6.0)	1577 (1022, 2131)	9 (8, 11)	5 (3, 8)	1591 (1034, 2149)
2. Case agreement	26.2 (22.5, 30.0)	4830 (3596, 6064)	0 (0, 1)	143 (120, 165)	4973 (3716, 6230)
3. Pre-testing	5.5 (3.1, 7.9)	883 (583, 1182)	52 (43, 61)	21 (9, 33)	956 (635, 1276)
4. Follow-up	5.4 (2.3, 8.6)	1910 (591, 3229)	3044 (3044, 3044)	3 (2, 4)	4957 (3637, 6277)
CAR-T prep & administration (steps 5–9)	132.1 (71.5, 192.8)	9058 (4459, 13,656)	3031 (2990, 3071)	251 (120, 381)	12,339 (7570, 17,108)
5. Catheter placement	4.3 (2.2, 6.4)	569 (354, 784)	1724 (1724, 1724)	8 (4, 12)	2301 (2083, 2520)
6. Leukapheresis	4.8 (3.9, 5.6)	668 (586, 750)	1171 (1165, 1177)	55 (16, 93)	1894 (1768, 2020)
7. Bridging therapy	3.2 (1.8, 4.6)	423 (306, 541)	18 (17, 19)	8 (3, 14)	450 (326, 574)
8. Lymphodepleting chemotherapy	9.6 (6.5, 12.8)	827 (626, 1027)	57 (36, 78)	27 (10, 45)	911 (672, 1149)
9. CAR-T infusion	110.3 (57.1, 163.4)	6571 (2587, 10,555)	60 (48, 73)	152 (87, 218)	6783 (2722, 10,845)
Acute management (first 30 days), (step 10) ^†	290.8 (156.7, 424.8)	17,665 (6690, 28,639)	665 (317, 1014)	751 (335, 1166)	19,080 (7342, 30,819)
Long-term management (steps 11–13)	8.5 (4.0, 13.1)	1123 (836, 1410)	88 (84, 92)	18 (8, 28)	1229 (929, 1530)
11. 30-day follow-up	2.6 (1.1, 4.1)	300 (211, 389)	10 (9, 11)	5 (2, 8)	315 (222, 408)
12. 60-day follow-up	2.5 (1.1, 4.0)	288 (211, 365)	10 (9, 11)	5 (2, 8)	303 (221, 384)
13. 90-day follow-up	3.4 (1.8, 5.0)	535 (415, 656)	69 (67, 71)	8 (4, 12)	612 (486, 738)

† Estimates reflect the proportion of the patient population estimated to experience each acute event. Categories are not mutually exclusive.

CAR-T: Chimeric antigen receptor T-cell.

Table 3. Summary of critical success factors and perspectives, by stakeholder type.

Critical success factors	Clinicians (n = 6)	Financial/operational personnel (n = 4)	Coverage/reimbursement decision-makers (n = 3)
Perceived CAR-T therapeutic efficacy	Consensus: favorable perceptions		Two of three stakeholders considered reported real-world CAR-T efficacy to be lower than that observed in clinical trials
Perceived adequacy of current CAR-T reimbursement levels	Consensus: perception of inadequate reimbursement All stakeholders noted that reimbursement for commercially insured patients exceeds that for Medicare; five of six stakeholders noted that Medicare cases are negative-margin services	Consensus: perception of inadequate reimbursement All stakeholders noted that reimbursement for commercially insured patients exceeds that for Medicare, with inpatient Medicare cases consistently negative-margin services	Not assessed
Preference for manufacturer-provided health economic data	Consensus: in favor of robust clinical health economic data to inform treatment selection and support reimbursement		Consensus: in favor of robust clinical and health economic data to inform coverage and reimbursement
Preference for CAR-T therapy setting of care	Consensus: preference for outpatient treatment, driven by reduced burden on facility resources, anticipated positive correlation with enhanced CAR-T therapeutic safety profiles, and more favorable reimbursement-based financial margins	Consensus: preference for outpatient treatment, driven by projected efficiencies in resource utilization and reimbursement-based financial margins	No consensus: Two of three stakeholders indicated that outpatient treatment would be preferable if associated with no difference in adverse events and long-term outcomes
Importance of prior CAR-T expertise to current success	Consensus: feedback noting that current success is directly informed by experience gained from clinical trials and early commercialized therapeutic use		No consensus: However, IDN stakeholder indicated that current CAR-T providers in their network were highly experienced
Perceived tolerance for non-fee-for-service CAR-T reimbursement models	Consensus: feedback indicated that stakeholders would be willing to participate in value-based agreements if reimbursement levels were set to ensure that positive clinical outcomes were sufficiently reimbursed to ensure positive margins	Consensus: feedback indicated that stakeholders support value-based agreements or risk-sharing if reimbursement levels were increased and timelines for assessed outcomes were reasonable	Consensus: feedback indicated that stakeholders are open to considering value-based agreements, risk-sharing outcomes-based contracting or capitated provider payments.

CAR-T: Chimeric antigen receptor T-cell; IDN: Integrated delivery network.

Table 4. Success factors incorporated process map summary^†.

Component (step)	Time (h): mean (min, max)	Personnel cost (USD$): mean (min, max)	Equipment cost (USD$): mean (min, max)	Physical plant cost (USD$): mean (min, max)	Total cost (USD$): mean (min, max)
Totals	404.7 (211.1, 606.8)	31,197 (14,238, 48,157)	6886 (6487, 7285)	1071 (500, 1643)	39,154 (21,225, 57,085)
Screening (steps 1–4)	36.9 (27.1, 46.7)	6822 (4205, 9438)	3106 (3095, 3116)	143 (112, 174)	10,070 (7412, 12,728)
1. Pre-screening	4.3 (2.7, 6.0)	1577 (1022, 2131)	9 (8, 11)	5 (3, 8)	1591 (1034, 2149)
2. Case agreement	21.7 (19.0, 24.3)	2452 (2008, 2897)	0 (0, 0)	114 (98, 129)	2566 (2106, 3026)
3. Pre-testing	5.5 (3.1, 7.9)	883 (583, 1182)	52 (43, 61)	21 (9, 33)	956 (635, 1276)
4. Follow-up	5.4 (2.3, 8.6)	1910 (591, 3229)	3044 (3044, 3044)	3 (2, 4)	4957 (3637, 6277)
CAR T-cell prep & administration (steps 5–9)	50.2 (23.3, 122.2)	5588 (2506, 8669)	3026 (2990, 3064)	160 (46, 275)	8774 (5542, 12,008)
5. Catheter placement	4.3 (2.2, 6.4)	569 (354, 784)	1724 (1724, 1724)	8 (4, 12)	2301 (2083, 2520)
6. Leukapheresis	4.8 (3.9, 5.6)	668 (586, 750)	1171 (1165, 1177)	55 (16, 93)	1894 (1768, 2020)
7. Bridging therapy	3.2 (1.8, 4.6)	423 (306, 541)	18 (17, 19)	8 (3, 14)	450 (326, 574)
8. Lymphodepleting chemotherapy	9.6 (6.5, 12.8)	827 (626, 1027)	57 (36, 78)	27 (10, 45)	911 (672, 1149)
9. CAR T-cell infusion	46.6 (8.9, 92.8)	3101 (634, 5568)	56 (48, 65)	62 (12, 112)	3219 (694, 5745)
Acute management (first 30 days) (step 10) ^†	290.8 (156.7, 424.8)	17,665 (6690, 28,639)	665 (317, 1014)	750 (335, 1166)	19,081 (7342, 30,819)
Long-term management	8.5 (4.0, 13.1)	1123 (836, 1410)	88 (85, 92)	18 (8, 28)	1229 (929, 1530)
11. 30-day follow-up	2.6 (1.1, 4.1)	300 (211, 389)	10 (9, 11)	5 (2, 8)	315 (222, 408)
12. 60-day follow-up	2.5 (1.1, 4.0)	288 (211, 365)	10 (9, 11)	5 (2, 8)	303 (221, 384)
13. 90-day follow-up	3.4 (1.8, 5.0)	535 (415, 656)	69 (67, 71)	8 (4, 11)	612 (486, 738)

† Estimates reflect the proportion of the patient population estimated to experience each acute event. Categories are not mutually exclusive.

CAR-T: Chimeric antigen receptor T-cell.