Efficacy and Safety Study of Chimeric Antigen Receptor-T Cell Therapy for People with Relapsed/Refractory Follicular Lymphoma

Although follicular lymphoma (FL) is an indolent lymphoma, it is prone to multiple recurrences and has a poor prognosis for progression of disease within 24 months (POD24) patients. To improve outcomes for patients with relapsed/refractory follicular lymphoma (R/R FL), we evaluated the efficacy and safety of Chimeric Antigen Receptor-T (CAR-T) cell therapy in these patients.

This retrospective study included 12 patients with R/R FL receiving CAR-T cell therapy from January 2017 to December 2023 in the First Affiliated Hospital of Soochow University who have consented to be included in our two clinical trials of CAR-T therapy. These two trials were registered at ClinicalTrials.gov, NCT03196830, NCT04539444.

The median age of the 12 patients was 46 (range, 28-59) years. Eight (66.7%) patients were male and four (33.3%) were female. FLIPI≥3 was present in 6 (50%) patients, and there were 7 (58.3%) patients with POD24. All patients received at least two lines of prior therapy. Eight (66.7%) patients received CD19 single-targeted CAR-T cell infusion and four (33.3%) patients received CD19/CD22 dual-targeted CAR-T cell infusion.

At 1 month after CAR-T cell infusion, the overall response (OR) and complete response (CR) rates for R/R FL patients were 12/12 (100.0%) and 9/12 (75.0%), respectively. By the cut-off date on March 7, 2024, the median follow-up time was 21.9 (range, 6.6-59.8) months. No deaths occurred. 10 (83.3%) patients continued their responses. 2 (16.7%) patients had progressive disease after 9 and 5 months. The 2-year progression-free survival (PFS) and overall survival (OS) rates were 82.5% and 100.0%, respectively. In a subgroup analysis, the CR rate of patients in the POD24 group did not show a significant difference from that of the non-POD24 group (71.4% vs. 80.0%, p=0.735), and the estimated 2-year PFS rate of patients in the POD24 and non-POD24 groups did not show a significant difference (82.5% vs. 83.3%, p=0.964).

Only 2 (16.7%) patients had grade 3 cytokine release syndrome (CRS), which was resolved by glucocorticoid. No immune cellular-associated neurologic syndrome (ICANS) or treatment-related death occurred.

In conclusion, patients with R/R FL treated with CAR-T cell achieved durable response with favorable safety profile. The long-term efficacy and safety need to be confirmed in larger clinical trials and longer follow-up period.

Keywords: chimeric antigen receptor-T cell therapy, relapsed/refractory follicular lymphoma, outcome, progression of disease within 24 months

No relevant conflicts of interest to declare.