Table 1

Considerations for outpatient infusion of CAR-T cell therapy

Factor category	Factor to be assessed	Specific considerations
Disease/clinical	Preinfusion LDH*	Subgroups defined for tisagenlecleucel: normal/low; high: 1–2×ULN, high: over 2×ULN†; subgroups as defined for lisocabtagene maraleucel: > or <500 U/L.‡
	Metabolic tumor volume*	Patients considered high-risk due to tumor bulk >10 cm.§
	Preinfusion CRP*	High CRP was associated with worse OS, but not PFS, in univariate Cox regression analysis.† High CRP associated with CRS and NE, and is lower in patients with durable response.‡
	Preinfusion ferritin*	High ferritin was associated with worse OS, but not PFS, in univariate Cox regression analyses.† High CRP associated with CRS and NE, and is lower in patients with durable response.‡
	ECOG PS*	ECOG PS 2–4 was associated with inferior outcomes.¶
	Presence of secondary CNS disease, multiple comorbidities and age ≥65 years	Outpatient administration for these otherwise clinically challenging patients should be considered since risk of complications is not increased in these patient populations.**, ††, ‡‡, §§, ¶¶
	Disease burden	Outpatient administration may not be suitable for patients with serious concurrent infection (eg, invasive fungal disease) or presence of cytopenias with fever.
Patient	Capability of patients to return to the hospital for fever	Willingness, understanding and ability to return to the medical center with concerning signs and symptoms.
	Socioeconomic support
	Patient’s proximity to the treating institution
	Patient’s preference for outpatient versus inpatient infusion	Outpatient therapy allows a return to ‘normalcy’.
	Reimbursement policies	Coverage variation between insurance types. Private—reimbursement is frequently approved. Public—reimbursement is based on the services provided, which vary between inpatient and outpatient infusion. Reimbursement implications need to be clarified/improved. Variation concerning whether outpatient treatment will be beneficial to both patients and institution. Rules for reimbursement are constantly evolving.
Institutional	Multidisciplinary team training	Proper institutional training and safeguards for the patient, physician (including on-call physicians), the infusion center and emergency department personnel.
	Multidisciplinary team communication plan	Communication with clinical, emergency department and any other on-call personnel at the treatment facility. May be the point of first contact to manage adverse events.
	Reimbursement policies	Institutions are better positioned to avoid losses with outpatient infusion (overall cost-to-charge ratio, degree of price markups, option for outlier payments). Reimbursement implications need to be clarified/improved. Variation concerning whether outpatient treatment will be beneficial to both patients and institution.

Although consideration of these factors is important for predicting safety outcomes, these factors are not 100% predictive.
*Associations with elevated level/scores and increased incidence or greater severity of CRS and/or NE have beed reported.
†Westin et al.3
‡Siddiqi et al.42
§Nastoupil et al.2
¶Jacobson et al.39
**Pasquini et al.10
††Bennani et al.44
‡‡Frigault et al.45
§§Kilgore et al.46
¶¶Kittai et al.47
CAR-T, chimeric antigen receptor T-cell; CNS, central nervous system; CRP, C reactive protein; CRS, cytokine release syndrome; ECOG PS, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; NE, neurological events; OS, overall survival; PFS, progression-free survival; ULN, upper limit of normal.