CAR22 Delivers Breakthrough Results in Small MCL/FL Cohort

Objective responses to treatment with CD22-directed chimeric antigen receptor (CAR) T-cell therapy (CAR22) were observed in the first four consecutive patients with relapsed or refractory mantle cell lymphoma (MCL) and follicular lymphoma (FL) in a phase 1b study. The patients who were treated did not have significant toxicity, according to study results.¹

A phase 1 study (NCT04088890) conducted among patients with large B-cell lymphoma (LBCL) progressing after CD19-directed CAR T-cell therapy laid the groundwork for the phase1b research. In the phase 1 study, CD22 was identified as an immunotherapeutic target for patients with LBCL after C10 progression, warranting long-term efficacy and safety investigation in multiple patient populations.²

The phase 1b study of relapsed and refractory MCL evaluated manufacturing feasibility, maximum tolerated dose of CAR22, and overall response rate (ORR) as co-primary endpoints. The secondary endpoints of the study were progression-free survival, overall survival, and duration of response.¹

The patients assessed were 18 years of age and older. In the FL cohort, patients were required to have histologically confirmed relapsed or refractory FL after two or more lines of systemic therapy or to have experienced relapse or progression within 24 months of initial chemotherapy. For the FL cohort, prior treatment must have included an anti-CD20 monoclonal antibody combined with systemic therapy. In the MCL cohort, eligible patients were those with histologically confirmed relapsed or refractory MCL after two or more prior lines of therapy. Prior therapy in the MCL group must have included a Bruton tyrosine kinase inhibitor, alkylating agent, and a CD20-targeted therapy. All patients who had prior CAR T-cell therapy had their most recent CAR T-cell infusion at least 30 days earlier and had five or fewer CAR-positive cells.

Dosed with CAR22 at 1 × 10⁶ CAR+ T cells/kg, the ORR at day 28 was 100%, and three patients achieved a complete response. One patient with relapsed or refractory MCL had a radiographic partial response to CAR22. By day 14, circulating CAR22 cells resulted in robust expansion (peak range, 47–1586 cells/μL), according to the study investigators.

The phase 1b study is ongoing, and investigators are currently looking to enroll more patients, including those with hairy cell leukemia, lymphoplasmacytic lymphoma, Burkitt lymphoma, and marginal zone lymphoma.

References

1. Kramer A, Srinagesh H, Su Y, et al. CD22-directed CAR T-cell therapy achieves complete remission in CD19-directed CAR T-cell refractory follicular and mantle cell lymphoma. Abstract #2064. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.
2. Frank M, Baird J, Kramer A, et al. CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study. Lancet. 2024;404(10450):353-363. doi: 1016/S0140-6736(24)00746-3