Academic CD19-Directed CAR-T Therapy Shows 86.7% ORR in Follicular Lymphoma

An academic CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has produced an 86.7% (13 patients) objective response rate (ORR) in a study of 15 patients with follicular lymphoma.¹ The data were presented in a poster at the European Hematology Association (EHA) 2025 Congress, held June 12 to 15, both virtually and in Milan, Italy, by Katsiaryna Zharkova, of N. N. Alexandrov National Cancer Centre of Belarus.

Out of the 13 patients who responded to the CAR-T product, 11 patients (73.4%) achieved a complete response (CR) and 2 patients (13.3%) achieved a partial response. The 2 patients who did not achieve a response (13.3%) experienced disease progression. Furthermore, the overall survival (OS) for the 15 treated patients was 93% at a median follow-up of 11.7 months. Zharkova and colleagues reported that progression-free survival was 80%. At a median follow-up of 11.7 months, event-free survival was 80%±14% (13 without events).

“In the group of patients who received second-line therapy, 2 patients had a CR, 1 patient had a partial response, which became complete after 6 months,” Zharkova and colleagues wrote in the poster.¹ “All patients who received first-line treatment achieved a CR and are currently alive without disease progression.”

With regard to safety, it was reported that 13% of patients experienced grade 1 cases of cytokine release syndrome (CRS), 13% of patients experienced grade 2 cases of CRS, and 7% experienced grade 3 CRS. The other 67% of patients did not experience CRS. Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 8% of patients, grade 2 ICANS was reported in 15% of patients, and grade 4 ICANS occurred in 8% of patients. The remaining 69% of patients did not experience ICANS. There were no grade 5 cases of CRS or ICANS in the study.

“The structure of the receptor includes scFv from the FMC63 antibody as an ectodomain, a transmembrane domain taken from the human CD28 protein, a costimulatory domain - 4-1BBL, and a CD3 signaling domain,” Zharkova and colleagues wrote of the CAR-T product’s design.¹

The group of 15 treated patients included 9 men and 6 women whose ages ranged from 30 to 66 years (median, 37). Eastern Cooperative Oncology Group performance status ranged from 0 to 1 for 93.4% of the patients. Three of the patients were administered the CAR-T as a first-line treatment. Three patients received the CAR-T as a second-line treatment; it was noted that these 3 patients had disease progression within 24 months of diagnosis and had disease that was refractory to both a CD20-targeting agent and an alkylator. The remaining 9 patients were treated with the CAR-T in third line.

“Academic anti-CD19 CAR-T cell therapy has demonstrated efficacy and safety in patients with relapsed/refractory (r/r) follicular lymphoma, including its use in second line therapy in high-risk patients,” Zharkova and colleagues concluded.¹

Notably, multiple FDA-approved CD19-directed CAR-T therapy products are currently available for the treatment of follicular lymphoma. Among these are Bristol Myers Squibb’s lisocabtagene maraleucel (liso-cel, marketed as Breyanzi) and Kite Pharma’s axicabtagene ciloleucel (marketed as Yescarta).^2,3 In January of 2025, a Type II variation application for liso-cel received a recommendation for approval in r/r follicular lymphoma from the European Medicines Agency's Committee for Medicinal Products for Human Use. Specifically, the recommendation pertains to a potential indication for adults with r/r FL who have received 2 or more prior lines of systemic therapy.

REFERENCES
1. Zharkova K, Konoplya N, Kalenik V, et al. Efficacy and safety of academic anti-CD19 CAR-T cell therapy for relapsed/refractory follicular lymphoma. Presented at: EHA 2025 Congress, June 12-15, virtual and in Milan, Italy. Abstract #PF912
2.Bristol Myers Squibb receives positive CHMP opinion for CAR T Cell Therapy Breyanzi for relapsed or refractory follicular lymphoma. News release. Bristol Myers Squibb. January 31, 2025. Accessed June 12, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Receives-Positive-CHMP-Opinion-for-CAR-T-Cell-Therapy-Breyanzi-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx
3. FDA approves axicabtageneciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA; April 1, 2022. Accessed June 12, 2025. https://bit.ly/3iSQ8XT