LAUSR

TO THE EDITOR: Chimeric antigen receptor (CAR) T-cell therapies are adoptive cell immunotherapies that have led to remarkable patient outcomes and transformed the treatment landscape in relapsed or refractory (R/R) B-cell malignancies and multiple myeloma [1–5]. Currently, 6 CAR T-cell products are approved by the Food and Drug Administration (FDA): tisagenlecleucel (tisa-cel; Kymriah®), axicabtagene ciloleucel (axi-cel; Yescarta®), brexucabtagene autoleucel (brex-cel; Tecartus®), lisocabtagene maraleucel (liso-cel; Breyanzi®), idecabtagene vicleucel (ide-cel; Abecma®), and ciltacabtagene autoleucel (cilta-cel; Carvykti®). These therapies have brought new challenges in the management of potentially life-threatening toxicities such as cytokine release syndrome (CRS) and CAR T-cell-related encephalopathy syndrome (CRES) or immune effector cell-associated neurotoxicity syndrome (ICANS). Consequently, models of CAR T-cell therapy evolved from clinical trials in which an inpatient setting was mandated for close monitoring and management of possible adverse events. Product acquisition costs and current reimbursement structures make inpatient cellular therapy administration challenging [6]. Outpatient administration is attractive as a primary model of cellular therapy administration [7]. Here, we share our experience in the development of an outpatient model for CAR T-Cell therapy and the results of our first 21 patients infused as outpatients with four different CAR T-cell products. In our institution, we structured our CAR T-cell program to be primarily an outpatient program from its inception. The Table 1 summarizes the development of our outpatient program with a focus on 8 essential components––creating a multidisciplinary team, training clinically competent nursing staff, alerting and educating providers in the community, augmenting patient knowledge and support, acquiring physical space, adhering to policies and procedures, financial review, and continuous review of outcomes and procedures. Outpatients were monitored after cell infusion in our outpatient oncology admission-pending unit (APU) with daily provider visits on days 1–14 then three times per week on days 15–28. Supplemental Fig. 1 shows a flow diagram of our cellular therapy process preand post-infusion. Supplemental Fig. 2 demonstrates our cellular therapy manufacturing process. The Supplemental Material also contains checklists that were provided to our infusion nurses for administration and monitoring of CAR T-cell therapy (Supplemental Table 1) and instructions for the triage nurses answering our cellular therapy phone line, available 24 h a day, seven days a week (24/7) (Supplemental Table 2). Within the first two years of the program, 23 patients (22 adults and one child) received commercially available cellular therapy products (Supplemental Table 3). Twenty-one of 23 (91%) were infused on an outpatient basis: 13 received axi-cel (12 for diffuse large B-cell lymphoma (DLBCL), and one for follicular lymphoma (FL)), six received tisa-cel (three for acute lymphoblastic leukemia (ALL) and three for DLBCL), one received brex-cel for mantle cell lymphoma (MCL), and one received liso-cel for DLBCL. Two patients receiving axi-cel were infused while inpatient based on physician consensus for high disease burden and co-morbidities. Of the 21 outpatients, 15 (71%) were admitted within 30 days after infusion, of whom five were admitted within 72 h. No patient required a visit to the emergency room. Median days to admission was four (range 1–28) and median days admitted was eight (range 1–30). Indications for admission were fever in 13 cases (87%) and neurological symptoms in two cases (13%). Of 12 (57%) patients with CRS, one had grade 3. Of six (29%) patients with neurotoxicity, one had grade 3. Seven patients (33%) received tocilizumab with a median of one dose (range 1–5) and seven received dexamethasone for a median duration of two days (range 1–21). There were no treatment-related deaths among those infused as outpatients. The overall response rate (ORR) was 76% (10 of 13 patients) with axi-cel (nine complete responses (CR) and one partial response (PR)), 100% with tisa-cel (five CR and one PR; all three ALL patients were negative on minimal residual disease (MRD) testing) and a CR in one patient with brex-cel. Two of the ALL patients received allogenic stem cell transplantation for consolidation after achieving MRD negative status with CAR T-cell therapy. The patient who received liso-cel had progression of disease on his one-month scan. At six months, 62% (8 of 13), 75% (four of six) and 100% (one of one) of these patients continued to respond with axi-cel, tisa-cel, and brexcel, respectively. The toxicity profile, responses, and death rates of the patients who received the four commercial products as outpatients are detailed in Supplemental Table 4. There are only a few published reports of outpatient CAR T-cell therapy for select products such as tisa-cel and liso-cel [8]. Initially, outpatient infusions were reported using the tisa-cel product in 18 of 75 patients (24%) treated for B-cell ALL in the ELIANA study [3], and 27% of patients treated for DLBCL in the JULIET study [2]. The University of Pennsylvania reported safe and feasible outpatient administration of the tisa-cel product with an admission rate of nine of 29 (31%) patients with a median of five days after infusion [9]. Additionally, Bachier et al. reported that patients could be safely monitored in the outpatient setting after receiving liso-cel [10]. Only 22 of 37 (59%) patients required hospitalization post-infusion with a median time to hospitalization of 5.5 days. Only three (8%) patients were hospitalized within three days of infusion [10]. Although it is difficult to compare across trials, the liso-cel and tisa-cel products are generally considered to have better toxicity profiles with lower incidence of CRS (42% [4] and