UF-Kure19 CAR-T Cell Therapy Demonstrates High CR Rates, Low Toxicity in R/R NHL

Treatment with UF-Kure19, a rapidly manufactured CAR T-cell therapy, led to complete responses (CR) and low toxicity in patients with relapsed/refractory non-Hodgkin lymphoma, according to data from a single-arm, mult-center phase 1 study (NCT05400109) presented at the 2024 ASH Annual Meeting.

Findings from the primary analysis showed that 80% of treated patients (n = 10) achieved a CR, and the remaining 2 patients experienced stable disease (SD).

“Naive/early memory CAR T-cell–enriched products may enhance in vivo proliferation, improve durability of response, and lead to better safety profiles,” lead study investigator David Wald, MD, PhD, explained. Wald is a professor in the Department of Pathology in the School of Medicine, co-leader of the Immune Oncology Program at Case Comprehensive Cancer Center, and associate director of the Medical Scientist Training Program in the School of Medicine at Case Western Reserve University in Cleveland, Ohio.

Among treated patients, 20% experienced cytokine release syndrome (CRS). Neurotoxicity occurred in 10% of UF-Kure19–treated patients. All CRS and neurotoxicity events resolved to grade 1 or less within one day.

The UF-Kure19 CAR-T therapy utilizes an ultra-fast manufacturing workflow, significantly reducing production time compared with traditional CAR T-cell therapies. The standard manufacturing process, which typically requires 7 to 14 days, involves apheresis, T-cell isolation, activation, gene transfer, and expansion before formulation.

“A PBMC-based rapid CAR T-cell therapy manufacturing process has the potential to address many key limitations of CART-cell therapy for NHL patients,” Wald explained.

In contrast, the UF-Kure19 process achieves CAR-T generation in less than one day using a simplified workflow that omits the need for T-cell isolation and expansion, streamlining production and improving scalability. This approach enables a highly efficient and cost-effective manufacturing process that can be applied across a broad range of CAR T-cell therapies targeting both solid and hematologic malignancies.

Preclinical data demonstrated that UF-Kure19 CAR T-cells exhibited markedly enhanced in vivo proliferation. Compared with products manufactured over a conventional 9-day period, UF-Kure19 cells generated via a 20-hour workflow demonstrated over a 100-fold increase in proliferation in mouse tumor models.

The phase 1 trial is a single-arm, open-label study evaluating the rapidly manufactured CAR T-cell therapy for patients with relapsed/refractory non-Hodgkin lymphoma. Eligible patients are required to have histologically confirmed disease after at least 1 prior systemic therapy. Lymphoma subtypes included mantle cell lymphoma (n = 2), follicular lymphoma (n = 4), diffuse large B-cell lymphoma (DLBCL; n = 3), and plasmablastic lymphoma (n = 1). The enrolled population had a median age of 64.5 years (range, 50-83) and had received a median of 1.5 prior lines of therapy (range, 1-7).

Upon enrollment, patients underwent lymphodepleting chemotherapy with fludarabine and cyclophosphamide administered over three consecutive days (–4 to –2) prior to the infusion of the CAR T-cell therapy on day 0.

The trial’s primary objective was to assess safety and tolerability. Secondary objectives include overall response rate, CR rate, and duration of response.

“Additional clinical testing is required to validate and expand upon the initial results observed with UF-Kure19,” Wald concluded.

Reference

Deng C, Caimi PF, Farooq U, et al. Phase I study results of UF-Kure19, a CAR-T product manufactured in less than 1 day, in patients with relapsed/refractory non-Hodgkin’s lymphoma. Blood. 2024;144(suppl 1):94. doi.org/10.1182/blood-2024-206596