Outpatient Reinfusion of CAR-T Cesnicabtagene Autoleucel (ARI0002h) in Multiple Myeloma Is Feasible and Safe
Authors: Merchán Muñoz Beatriz , Martínez-Roca Alexandra , Ballestar Nuria , Gallego Cristina , Martínez-Cibrián Nuria , Ortiz-Maldonado Valentin , Rodriguez-Lobato Luis Gerardo , Albiol Nil , Ayora Pilar , Ramos Carla , Sanchez-Castañon Maria , Juan Manel , Delgado Julio , Esteve Reyner Jordi , Urbano-Ispizua Alvaro , Fernández de Larrea Carlos , Fernández-Avilés Francesc 
Published: December 2024

INTRODUCTION
Cesnicabtagene autoleucel (cesni-cel; ARI0002h) is a fully academic, autologous, 4-1BB based second generation and humanized B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma (MM) that has shown safety and efficacy in the CARTBCMA-HCB-01 clinical trial. After 3 months from the initial dose, patients who remain in response, have not developed severe complications, and have an additional dose available, receive a reinfusion of 3x106 CAR-T cells/kg, with or without prior lymphodepletion (LD) (fludarabine 30 mg/m2 plus cyclophosphamide 300 mg/m2 for three days on days -6 to -4), depending on the absence or presence of circulating CAR-T cells, respectively. Previously, this reinfusion was performed on 24 patients within the trial, requiring a median hospitalization of 4 days without severe complications.
Leveraging our extensive expertise in managing high-complexity procedures at home, we initiated an outpatient CAR-T reinfusion program in September 2023.
METHODS
Between September 2023 and July 2024, 15 patients with MM who required cesni-cel reinfusion and met the inclusion criteria were enrolled. The eligibility criteria for the outpatient CAR-T reinfusion program included ECOG performance status ≤2, travel time from home to the hospital &lt;30 minutes, 24-hour trained caregiver availability, absence of active toxicities grade ≥2 and voluntary acceptance. This outpatient program involves administering the outpatient reinfusion and providing immediate follow-up at home.
The outpatient program begins with a medical and nursing visit from the Home Care Unit (HCU), focusing on specific therapeutic education for the patient and their caregiver. Tools for detecting symptoms and warning signs are provided, along with a detailed action plan for adverse events.
Home LD was scheduled for patients who required it. Reinfusion was administered intravenously, preferably through a peripheral venous catheter. After 1 hour of observation, the patients were monitored at home with their trained caregiver. Vital signs and immune effector cell-associated neurotoxicity (ICAN) score were checked via telephone by nursing staff every 12 hours, with analytical tests performed on days +1 and +3 following the reinfusion.
RESULTS
Fifteen patients were included in the program, accomplishing all inclusion criteria. The median age was 59 years (range, 49-75), and 53% were women. All patients had an ECOG performance status of 0-1. Six patients (40%) exhibited high-risk cytogenetics, and 2 patients (13%) had extramedullary involvement prior to receiving CAR-T therapy. Thirteen patients (86%) had previously undergone autologous transplantation and 85% of the patients had received 3 or more lines of previous treatment. Eleven patients (93%) required bridging chemotherapy before CAR-T therapy, with 6 (46%) receiving cyclophosphamide-dexamethasone regimen.
Four (26.6%) patients required prior LD due to the absence of detectable ARI0002h in peripheral blood by PCR at the time of reinfusion. The median home follow-up was 4 days (range, 3-4) for patients not requiring LD and 10 days for those requiring LD. No cytokine release syndrome, ICANs, macrophage activation syndrome or other adverse events were observed during follow-up. Fifty percent of the patients who received LD developed grade 4 neutropenia, which resolved following the administration of colony-stimulating factors, with no other incidents. The remaining patients did not develop grade 4 cytopenias. There were no hospital readmissions or additional medical or nursing visits needed by the HCU.
Prior to reinfusion, 66% of the patients achieved a complete response, while 33% achieved a partial response. With a median follow-up of 73 days after reinfusion (range 15-291 days), 86% of the patients maintained their response post-reinfusion. Only two patients experienced a relapse after 6 months of receiving the reinfusion.
CONCLUSIONS
Outpatient reinfusion of cesni-cel is feasible and safe, allowing patients to remain in an outpatient setting throughout the procedure and optimizing hospital resources. The insights gained from this outpatient program will enable us to expand the indications for home management of patients treated with CAR-T.