LV20.19 CAR-T Produces 100% Overall Response Rate in Patients With R/R Mantle Cell Lymphoma

This interview originally appeared on our sister site, OncLive®.

Results from the phase 2 portion of a phase 1/2 trial (NCT04186520) published in the Journal of Clinical Oncology showed that the prespecified efficacy threshold for 90-day complete response (CR) rate was exceeded in patients with relapsed/refractory (r/r) mantle cell lymphoma (MCL) who were treated with an on-site manufactured, dual-targeted anti-CD20 and -CD19 CAR T-cell therapy (LV20.19).

At a fixed dose of 2.5 × 10⁶ cells/kg, treatment in the form of a single infusion of IL-7/IL-15–expanded LV20.19 CAR T-cells yielded a best overall response rate (ORR) of 100%, an 88% complete response rate, and a 12% partial response rate. Furthermore, disease relapse was recorded in only 2 patients at a median follow-up of 15.8 months. At this time point, the median progression-free survival and the median overall survival had not been reached.

With regard to safety, there were cases of cytokine release syndrome (CRS) reported in 94% of the patients. All cases were grade 1 or 2 in severity. In 18% of patients immune effector cell–associated neurotoxicity syndrome (ICANS) was reported, with 2 of the cases being deemed reversible grade 3 toxicities. There were 3 nonrelapse mortality events reported, with all having the context of ongoing B-cell aplasia.

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

Phase 1/2 Trial Design and Eligibility Criteria

The trial was designed to evaluated safety, efficacy, and manufacturing feasibility for LV20.19 in adults with r/r B-cell malignancies, and took the form of a single-arm, open-label study.

A confirmed diagnosis of MCL and had active, measurable disease constituted a requirement for the phase 2 cohort. Participants' disease was required to be r/r, with the definition of r/r corresponding to relapse after 2 prior lines of cytotoxic chemotherapy that included an antiCD20 antibody; progressive disease following at least 2 lines of BTK inhibitor therapy; relapse after autologous or allogeneic transplant; or relapse after having been treated previously with an antiCD19 CAR T-cell therapy. The maximum number of patients who previously were treated with antiCD19 CAR-T was limited to 4 participants by the investigators.

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