LV20.19 CAR T-Cell Therapy Yields 100% ORR in R/R Mantle Cell Lymphoma

Treatment with an on-site manufactured, dual-targeted anti-CD20 and -CD19 CAR T-cell therapy (LV20.19) exceeded the prespecified efficacy threshold for 90-day complete response (CR) rate in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) in the phase 2 portion of a phase 1/2 trial (NCT04186520), according to findings published in the Journal of Clinical Oncology.

Data showed that treatment with a single infusion of IL-7/IL-15–expanded LV20.19 CAR T cells at a fixed dose of 2.5 × 106 cells/kg resulted in a best overall response rate (ORR) of 100%, including a CR rate of 88% and a partial response rate of 12%. At a median follow-up of 15.8 months, only 2 patients experienced disease relapse; neither the median progression-free survival nor the median overall survival had been reached.

Cytokine release syndrome occurred in 94% of patients, all at grade 1 or 2, and immune effector cell–associated neurotoxicity syndrome (ICANS) was observed in 18%, including 2 cases of reversible grade 3 toxicity. Three nonrelapse mortality events occurred, all in the context of ongoing B-cell aplasia.

“We demonstrate that on-site adaptive manufactured LV20.19 CAR T cells are feasible, safe, and efficacious for [patients with] relapsed/refractory MCL with best ORR of 100%, a favorable safety profile, and few relapses to date,” lead study author Nirav N. Shah, MD, MS, and colleagues explained in the conclusion on his analysis. Shah is an associate professor of medicine in the Division of Hematology and Oncology at the Medical College of Wisconsin in Milwaukee.

Phase 1/2 Trial Design and Eligibility Criteria

The trial was a phase 1/2, single-arm, open-label study designed to evaluate the safety, efficacy, and manufacturing feasibility of LV20.19 in adult patients with R/R B-cell malignancies.

For the phase 2 cohort, eligible patients were required to have a confirmed diagnosis of MCL who had active, measurable disease. They needed to have relapsed or refractory disease, defined as relapse after 2 prior lines of cytotoxic chemotherapy including an anti-CD20 antibody; progressive disease after 2 or more lines of BTK inhibitor therapy; relapse following autologous transplant; relapse following allogeneic transplant; or relapse following prior anti-CD19 CAR T-cell therapy. Notably, investigators limited the maximum number of patients with prior anti-CD19 CAR T-cell therapy to 4 patients.

Key exclusion criteria included confirmed active HIV, hepatitis B, or hepatitis C infection; history of significant autoimmune disease or active, uncontrolled autoimmune phenomenon requiring steroid therapy of more than 20 mg prednisone or equivalent daily; and the presence of grade 3 or higher nonhematologic toxicities from prior treatment, unless attributed to underlying disease.

Patients receiving concurrent investigational agents or enrolled in another therapeutic trial were excluded, with a required washout period of at least 14 days or 5 drug half-lives (whichever was shorter) before apheresis. Investigators utilized an on-site CliniMACS Prodigy platform with a flexible 8- to 12-day manufacturing process to optimize the final CAR T-cell product for an increased proportion of naïve and stem cell memory–like T cells.

Manufacturing feasibility was also assessed with a fixed 12-day process and, in one study arm, with mandated cryopreservation prior to infusion. Patients in all arms received a fixed target dose of 2.5 × 106 CAR-20/19 T cells/kg.

The phase 2 MCL cohort was designed to determine the 3-month CR rate and confirm the feasibility of the flexible manufacturing approach.

Additional Safety Data

After no dose-limiting toxicities were reported during the phase 1 portion, the most common grade 3 or higher adverse effects in the phase 2 cohort included neutropenia (47%), anemia (29%), and thrombocytopenia (18%).

References

1. Shah NN, Colina AS, Johnson BD, et al. Phase I/II study of adaptive manufactured lentiviral anti-CD20/anti-CD19 chimeric antigen receptor T cells for relapsed, refractory mantle cell lymphoma. J Clin Oncol. 2025;43(20):2285-2295. doi:10.1200/jco-24-02158
2. CAR-20/19-T cells in patients with relapsed refractory B-cell malignancies. ClinicalTrials,gov. Updated February 18, 2025. Accessed August 8, 2025. https://clinicaltrials.gov/study/NCT04186520