CAR22 Therapy Safe and Effective in MCL, Follicular Lymphoma

Autologous CD22-directed chimeric antigen receptor T-cell (CAR22) therapy yields high safety and promising efficacy in patients with relapsed or refractory follicular lymphoma (FL) and mantle cell lymphoma (MCL), according to a phase Ib trial presented at the 2025 Tandem Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR.

Six patients received 1 × 10⁶ CAR+ T cells/kg, including three patients with FL and three with MCL. Eligible patients with FL experienced relapse after two or more lines of therapy or had progressive disease within two years of the first treatment. Eligible patients with MCL experienced relapse after two or more lines of therapy, including a Bruton tyrosine kinase inhibitor and immunochemotherapy. Five patients received prior CD19-directed CAR T-cell (CAR19) therapy.

The study’s primary outcomes were manufacturing feasibility, maximum tolerated dose, and overall response rate (ORR). Secondary outcomes include duration of response, progression-free survival, and overall survival; exploratory outcomes include CAR expansion.

Five of six patients experienced grade 1 or 2 cytokine release syndrome, with a median onset on day 1 and a median duration of two days. Immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome was observed in one patient and resolved after treatment with steroids and anakinra. No dose-limiting toxicities, immune effector cell–associated neurotoxicity syndrome, or grade 3 or higher nonhematologic toxicities were observed.

In terms of efficacy, CAR22 therapy demonstrated an ORR of 100% and a complete response rate of 83%. Peak CAR22 expansion occurred from days 10 to 14, with a range of 1.8 to 1,586 cells/μL, according to peripheral blood flow cytometry.

Reference

Srinagesh HK, Kramer AM, Hamilton MP, et al. CD22-directed CAR T-cell therapy achieves complete remission in CD19-directed CAR T-cell refractory follicular and mantle cell lymphoma with superior safety and absence of neurotoxicity. Abstract #524. Presented at the 2025 Tandem Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 12-15, 2025; Honolulu, Hawai’i.