Benjamin R, Jain N, Maus MV, et al. UCART19, a First-in-Class Allogeneic Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Adults with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia (CALM): A Phase 1,Dose-Escalation Trial. The Lancet Haematology. 2022; (doi: 10.1016/S2352-3026(22)00245-9).

A first-in-human study showed UCART19, an allogeneic genome-edited anti-CD19 chimeric antigen receptor (CAR) T-cell product derived from healthy donors, to be a safe treatment option for adults with relapsed or refractory B-cell acute lymphoblastic leukemia. Included in the Phase I trial were 25 patients aged 16-70 years with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia who exhibited morphological relapse or a minimal residual disease level of at least 1 x 10^-3, and who had exhausted standard treatment options. The trial involved a dose-escalation framework of up to three UCART19 dose levels of CAR T cells followed by safety evaluation and disease response assessments.   Lymphodepletion was accomplished with fludarabine (30 mg/m² per day intravenously for 3 days) and cyclophosphamide (500 mg/m² per day intravenously for 3 days) with or without alemtuzumab (1 mg/kg or 40 mg or 60 mg over 5 days). Patients then received I.V. UCART19 doses of 6 x 10⁶, 6-8 x 10⁷, or 1.8-2.4 x 10⁸ total CAR T cells. A total of 24 patients were enrolled and treated.  Dose-limiting toxicities developed in three patients, with one having grade 4 cytokine release syndrome and two having grade 4 prolonged cytopenias. Six had grade 3 or higher cytokine release syndrome and one had grade 3 or higher neurological toxicity. Seven patients experienced grade 3 or higher infections, while four had grade 4 prolonged cytopenia. Grade 1 acute cutaneous graft-versus-host disease developed in two patients. Nine of 14 patient deaths were due to progressive disease, and four of the five deaths caused by infections or other complications were attributed to UCART19, lymphodepletion, or both. The overall post-follow-up response rate was 48% at a median follow-up of 12.8 months. Additionally, the duration of response and median relapse-free survival, progression-free survival, and overall survival were 7.4 months, 2.1 months, and 13.4 months, respectively. The findings indicate that UCART19 allogeneic off-the-shelf CAR T cells have a manageable safety profile, have antileukemic activity and may be safely used in treatment of patients with relapsed B-cell ALL, the researchers report. 

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Tags: MRD, study, Outcomes, Treatment, Cellular therapy, Lymphoma, Allogeneic, ALL, Transplant, disease, CAR T-cell, CD19, acute lymphoblastic leukemia