Large B-cell lymphoma (LBCL) patients who have experienced disease progression following CD19-directed CAR T-cell therapy now have a new potential treatment option. A recent phase I trial, published in The Lancet, explored the efficacy of CD22-directed CAR T-cell therapy (CAR22) for these challenging cases.
The study, conducted at Stanford University, involved 40 patients between October 2019 and October 2022. All participants underwent leukapheresis, with CAR22 successfully manufactured and administered to 38 patients. These patients had either progressed after CD19-directed therapy or had CD19-negative disease.
Patients received lymphodepleting therapy followed by one of two dose levels of CD22 CAR T-cells. The maximum tolerated dose and the recommended phase II dose was identified as 1 × 10⁶ CAR-positive cells/kg. This dose was well-tolerated, with no severe dose-limiting toxicities. In contrast, a higher dose level showed some adverse effects, including reversible cardiac and liver issues.
The results were promising: 88% of the 38 patients showed an objective response, with 53% achieving a complete response. The median response duration was 27.8 months. Among those receiving the recommended dose, 66% responded, and 52% achieved complete remission.
These findings highlight CD22 as a viable immunotherapeutic target for LBCL and demonstrate the potential of CAR22 therapy for patients whose disease has progressed after previous CAR T-cell treatments. Further research is needed to confirm long-term efficacy and identify which patient groups will benefit most from this innovative approach.
