Expanding the boundaries of CAR T-cell therapy: Implementation of an outpatient-at-home (OATH) model

Abstract

Abstract Background: CAR-T cell immunotherapy represents a major advancement in the treatment of relapsed/refractory (R/R) hematologic malignancies. However, treatment-related toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), often requires inpatient care for effective monitoring and management. Building on our experience with complex at-home (AH) procedures, including both allogeneic and autologous hematopoietic stem cell transplantation (HCT), we developed an Outpatient-At-Home (OATH)CAR T-cell therapy model, within the framework of the academic CAR-T program in our center. This approach emphasizes structured care coordination, proactive toxicity management, and optimized resource use. Methods: In March 2024, we launched the OATH CAR T-cell program. Eligible patients (pts) were adults with R/R B-cell precursor acute lymphoblastic leukemia (BCP-ALL) or multiple myeloma (MM) who met predefined clinical criteria (ECOG 0–1, no active infections, availability of a trained caregiver, and low tumor burden). Pts and caregivers received pre-enrolment education, providing symptom detection tools, including the caregiver-performed immune effector cell encephalopathy (ICE) score and an adverse event action plan. The protocol included AH lymphodepletion with fludarabine (30 mg/m²/d) and cyclophosphamide (300 mg/m²/d) for three days, followed by fractionated infusions (10%, 30%, and 60%) of one of the academic CAR-T CD19-directed (varnimcabtagene autoleucel, ARI0001, 1x10⁶ CAR T cells/kg) or BCMA-directed (cesnicabtagene autoleucel, ARI0002h, 3x10⁶ CAR T cells/kg), depending on the underlying malignancy. Infusions were administered in a day care unit, with AH follow-up post-infusion. Pts were monitored via twice-daily telephone assessments for vital signs and ICE scores, along with AH evaluations and laboratory tests every 48–72 hours. A specialized 24-hour hematology support unit was available to manage urgent medical events. Toxicities were graded using American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria. Treatment responses were assessed via bone marrow morphology and minimal residual disease for BCP-ALL, and according to International Myeloma Working Group (MWG) criteria for MM. Results: Between March 2024 and June 2025, 18 pts were evaluated for inclusion. Of these, 17 pts (94.4%)—14 with BCP-ALL and 3 with MM—met inclusion criteria, while one patient (5.6%) did not proceed due to a psychiatric condition. The median age of the included pts was 41 years (range, 30–71), with a median of two prior treatment lines (range, 2–5). Prior allogeneic HCT was reported in 71% of BCP-ALL pts and prior autologous HCT in all MM pts. The median duration of AH follow-up was 21 days (range, 5–30). CRS only occurred in 2 pts (11.7%; both grade 1) and was effectively managed with tocilizumab (8 mg/kg) and dexamethasone (10 mg). ICANS occurred in 2 pts (11.7%; one grade 1 and one grade 4), both resolved within 24 hours after corticosteroid treatment (dexamethasone 10 mg, followed by rapid tapering), preventing intensive care unit (ICU) admission. Median onset of toxicity was day 6 post-infusion (range: 5–8). Four pts (23.5%) required hospitalization: one for grade 1 CRS with grade 3 transaminitis, two for ICANS, and one for grade 3 acute graft versus host disease (skin grade 3, lower gastrointestinal grade 3), related to prior allogeneic HCT. Median hospital stay was 8 days (range: 4–30). No ICU admissions or treatment-related deaths occurred. At a median follow-up of 155 days (range: 45–495), 15 pts (88.3%) achieved complete remission (12/14 BCP-ALL and 3/3 MM). One patient with BCP-ALL died due to a disease progression event and another BCP-ALL patient has experienced relapse. Conclusion: The OATH model for academic CAR T-cell therapy is feasible, safe, and effective for selected pts with R/R BCP-ALL and MM. This approach may reduce hospital admissions and optimize healthcare resource utilization while ensuring patient safety.