The Impact of Chimeric Antigen Receptor T Cell Quality to Clinical Safety and Efficacy in Non-Hodgkin Lymphomas

Background: Immunotherapy has become increasingly important in modern cancer treatments. It has become evident that chimeric antigen receptor-modified T (CAR-T) cells may be a promising treatment for hematological malignancies. Malignancies affecting B cells have been successfully treated using CAR-T cell therapies. Many studies have explored the influence of various factors on the efficacy and survival of CAR-T therapy from different aspects, including the patient's disease state, general condition, tumor burden, and even the dose of CAR-T cells infused. Few researchers have explored the effect of CAR-T cell quality on disease treatment impact on remission, survival, and prognosis. This study combines the essential condition of patients and quality data of CAR-T cells, such as transduction efficiency, killing efficiency, and the ratio of CD4+ and CD8+ subsets, to analyze CAR-T's safety and clinical efficacy in the treatment of non-Hodgkin's lymphoma in our center.

Methods: This was a retrospective, single-center, investigator-initiated study. A total of 179 patients with NHL were included. Patients' baseline data were obtained from electronic medical records and telephone follow-ups. Laboratories provided data on the quality of patients' CAR-T cells. We conducted a multivariate analysis to determine the independent factors that influence treatment response and patient prognosis.

Results: In our study, the median age of 179 NHL patients was 52 (range 17-78) years, and 51 (28.5%) were ≥60 years old. Before CAR-T treatment, 22 (12.3%) patients remained in complete remission (CR), and 83 (46.4%) patients were in progressive disease (PD). Among the available data, 105 (61.4%) patients had CAR-T cell killing efficiency (KE) <30%, while 66 (38.6%) patients had killing efficiency (KE) ≥30%. There were 101 (58%) patients with CAR-T cell transduction efficiency (TE) <40% and 73 (42%) with transduction efficiency (TE) ≥40%, respectively. CD4+/CD8+ ratio of CAR-T cells <1 in 32 (18.4%) patients and CD4+/CD8+ ratio of CAR-T cells ≥1 in 142 (81.6%) patients. Overall, the median event-free survival (PFS) was 10.6 months (95% CI: 4.064-17.136months), and the median overall survival has not yet been reached. The 6-month OS was 80.2%, and the 1-year OS was 70.6%. 2-year 0S is about 59.8%. In addition, we divided patients into different subgroups according to the TE and KE of CAR-T cells, and the results of multivariate logistic regression analysis were as follows. The subgroup with TE<40% had a higher complete remission rate than the subgroup with TE≥40%. And the subgroup with KE≥30% had a higher rate of complete remission than the subgroup with KE<30%, with p-values equal to 0.007 and 0.022, respectively. There was statistical significance, so TE and KE independently influenced efficacy factors. Multivariate cox regression analysis showed that the subgroup of CAR-T CD4+/CD8+<1 had better overall survival than CAR-T CD4+/CD8+≥1, p=0.039 (95% CI: 0.114-0.947). Therefore, the ratio of CAR-T CD4+/CD8+ was an independent factor for OS, while the subgroups of transduction efficiency and killing efficiency did not show statistical significance.

Conclusion: In general, CAR-T therapy has shown significant efficacy in NHL, and the quality of CAR-T cells plays a vital role in treatment. Screening suitable CAR-T cells in future treatment will Make the treatment effect more satisfactory.

No relevant conflicts of interest to declare.