Liso-cel treatment in the outpatient setting

Lisocabtagene maraleucel (liso-cel; JCAR017) is an investigational anti-CD19 chimeric antigen receptor (CAR) T-cell product administered at equal target doses of CD8⁺ and CD4⁺ CAR T cells. The administration of liso-cel in the outpatient setting is allowed based on the discretion of the investigator and needs to follow standardized guidelines for safety monitoring and management. Outpatient administration provides multiple advantages, including making CAR T-cell therapy more accessible.¹

During the American Society of Clinical Oncology (ASCO) Virtual Meeting 2020, Carlos Bachier¹ presented the results of a study evaluating the safety and efficacy of liso-cel in patients with relapsed/refractory large B-cell lymphoma (LBCL) who were monitored as outpatients at both university and non-university sites in three separate TRANSCEND studies: the phase I NHL-001 (NCT02631044) and the phase II OUTREACH (NCT03744676) and PILOT (NCT03483103) trials.

Methods

After lymphodepletion with fludarabine (30 mg/m²) and cyclophosphamide (300 mg/m²) for 3 days, liso-cel was administered at either 50 × 10⁶, 100 × 10⁶, or 150 × 10⁶ CAR T cells for patients recruited on the TRANSCEND NHL-001 study, or at 100 × 10⁶ CAR T cells on the PILOT and OUTREACH studies.

Patients were considered outpatients if they received liso-cel infusion in the outpatient or inpatient setting and if they left the clinic or were discharged from the hospital at the end of the observation period on the day of infusion. Patients were required to receive safety monitoring education, have a caregiver, and stay within a one hour travel time to the site of care for 30 days posttreatment. All study sites had a multidisciplinary CAR T-cell team and standard operating procedures for toxicity management and monitoring.

Results

At data cutoff, 59 patients were treated and/or monitored as outpatients across the three studies (TRANSCEND NHL 001, n = 25; OUTREACH, n = 22; and PILOT, n = 12). Baseline demographics, safety outcomes, and response are reported in Table 1.

Table 1. Patient characteristics, safety outcomes, and response¹

CR, complete response; CRS, cytokine release syndrome; DLBCL, diffuse large B-cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group performance status; FL3B, follicular lymphoma Grade 3B; HGBCL, high grade B-cell lymphoma; HSCT, hematopoietic stem cell transplant; NE, neurological event; ORR, overall response rate; PD, progressive disease; PMBCL, primary mediastinal B-cell lymphoma; PR, partial response; SD, stable disease; TEAE, treatment-emergent adverse event.
	Outpatients				Inpatients (n = 273)
	TRANSCEND NHL 001 (n = 25)	OUTREACH (n = 22)	PILOT (n = 12)	Total (n = 59)
Patient characteristics
Median age, years (range)	60 (24─82)	65 (50─83)	72 (58─80)	63 (24─83)	64 (18─86)
≥ 65, n (%)	7 (28)	11 (50)	10 (83)	28 (47)	127 (47)
Histology, n (%)
DLBCL not otherwise specified	14 (56)	17 (77)	7 (58)	38 (64)	136 (50)
DLBCL transformed from indolent histologies	5 (20)	5 (23)	0 (0)	10 (17)	78 (29)
HGBCL/PMBCL/FL3B	6 (24)	0 (0)	5 (42)	11 (19)	59 (22)
ECOG PS of 0─1/2 at screening, n (%)	25 (100)/0 (0)	22 (100)/0 (0)	9 (75)/3 (25)	56 (95)/3 (5)	263 (96)/10 (4)
Prior lines of therapy, median (range)	2 (1─5)	2 (2─5)	1 (1─1)	2 (1─5)	2 (1─8)
Prior HSCT, n (%)	9 (36)	7 (32)	0 (0)	16 (27)	10 (4)
Chemotherapy refractory, n (%)	16 (64)	16 (73)	6 (50)	38 (64)	184 (67)
Safety
TEAEs Grade 5, n (%)	0	0	0	0	8 (3)
CRS or NEs, n (%)
Any grade	15 (60)	10 (45)	0 (0)	25 (42)	124 (45)
Grade ≥ 3	2 (8)	1 (5)	0 (0)	3 (5)	29 (11)
CRS, n (%)
Any grade	12 (48)	9 (41)	0 (0)	21 (36)	111 (41)
Grade ≥ 3	1 (4)	0 (0)	0 (0)	1 (2)	5 (2)
NEs, n (%)
Any grade	11 (44)	6 (27)	0 (0)	17 (29)	75 (27)
Grade ≥ 3	2 (8)	1 (5)	0 (0)	3 (5)	27 (10)
Median time to CRS onset, days	—	—	—	5	4
Median time to NE onset, days	—	—	—	8	9
Median duration of CRS, days	—	—	—	5	5
Median duration of NEs, days	—	—	—	7	9
Tocilizumab or corticosteroid for CRS, n (%)
Tocilizumab only	0	0	0	0	28 (10)
Tocilizumab and corticosteroid	1 (4)	3 (14)	0	4 (7)	23 (8)
Corticosteroid only	2 (8)	0	0	2 (3)	3 (1)
Corticosteroids for NEs, n (%)	5 (20)	2 (9)	0	7 (12)	42 (15)
Best overall response, n (%)
ORR	20 (80)	16 (84)	11 (92)	47 (84)	189 (73)
CR	14 (56)	13 (68)	7 (58)	34 (61)	137 (53)
PR	6 (24)	3 (16)	4 (33)	13 (23)	52 (20)
SD	2 (8)	1 (5)	0 (0)	3 (5)	29 (11)
PD	3 (12)	2 (11)	1 (8)	6 (11)	28 (11)
Not evaluable	0 (0)	0 (0)	0 (0)	0 (0)	10 (4)

Hospitalization was required for 54% of outpatients, with a median length of stay of six days, and the main reasons for admission were cytokine release syndrome (CRS) and/or neurological events (17 patients) and other adverse events (15 patients). Two patients required treatment in the intensive care unit: one for CRS and one for dehydration.

Conclusion

The safety profile of liso-cel following outpatient administration showed no increase in rates of severe CRS or other adverse events when compared to inpatient administration. These data, together with the similar efficacy rates observed between the outpatient and inpatient settings, support outpatient liso-cel administration for patients with relapsed/refractory LBCL, provided that the proper safety monitoring and standard operating protcols are being followed. Outpatient administration and monitoring of liso-cel continue to be evaluated and further data are expected to further validate these results.