International Journal Publication | Prof. Xiaoyan Ke & Prof. Kai Hu's Team: CAR-T Cell Therapy Shows Promising Efficacy in TP53-Mutated R/R CNSL

Summary: Patients with relapsed/refractory central nervous system lymphoma (R/R CNSL) harboring TP53 mutations are often highly resistant to chemotherapy and have poor outcomes. A study by Prof. Xiaoyan Ke and Prof. Kai Hu's team at Beijing GoBroad Hospital, published in Frontiers in Medicine, analyzed data from 61 patients with R/R CNSL. Among patients with TP53 mutations who received CAR-T cell therapy, both the overall response rate and complete response rate reached 64.5%, comparable with outcomes in patients with wild-type TP53. Subgroup analysis also showed significantly longer survival in TP53-mutated patients with the non-GCB subtype. These findings provide new clinical evidence and a useful reference for CAR-T treatment in patients with high-risk genetic alterations.

Patients with relapsed/refractory central nervous system lymphoma (R/R CNSL) generally face poor outcomes, with prognosis varying considerably according to multiple factors. TP53 mutations are considered one of the key genetic factors associated with treatment outcome and have long posed a challenge in lymphoma care. In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has shown encouraging efficacy and safety in R/R CNSL. However, relatively little has been known about whether TP53 mutations affect response to CAR-T therapy, making this an important area for further study.

Recently, Dr. Danyang Li from the team led by Prof. Xiaoyan Ke and Prof. Kai Hu of the Department of Lymphoma and Myeloma at Beijing GoBroad Hospital published a study in Frontiers in Medicine entitled “CAR-T cell therapy in TP53-mutated CNS lymphoma: overcoming a high-risk genetic barrier.” The study offers new insights into the use of CAR-T cell therapy for patients with TP53-mutated R/R CNSL.

Prof. Kai Hu explained: “Relapsed/refractory central nervous system lymphoma can be particularly difficult to treat. When the disease remains sensitive to chemotherapy, patients may achieve remission and can often benefit from autologous hematopoietic stem cell transplantation. In real-world practice, however, many patients develop chemotherapy resistance after relapse, and TP53 mutations are common among these difficult-to-treat cases. To better understand this population, our team analyzed 61 patients with R/R CNSL, including 43 who received CAR-T cell therapy. We compared overall survival (OS) and progression-free survival (PFS) between patients with TP53 mutations (TP53+) and those with wild-type TP53 (TP53−), and also evaluated other factors associated with prognosis.”

Research Highlights

1. CAR-T Therapy Achieved Comparable Responses in TP53+ and TP53− R/R CNSL

The study showed that both the overall response rate (ORR) and complete response rate (CRR) were 64.5% in the TP53+ group. In the TP53− group, ORR and CRR were 73.3% and 69.2%, respectively, indicating broadly comparable response rates between the two groups. Median progression-free survival (PFS) was 12.77 months in the TP53+ group (95% CI: 6.33–∞), compared with 22.4 months in the TP53− group (95% CI: 6.13–∞); however, the difference was not statistically significant. These findings suggest that CAR-T cell therapy can also be effective for patients with TP53-mutated R/R CNSL.

2. TP53+ Non-GCB R/R CNSL May Derive Greater Benefit, With Significantly Longer Survival

Subgroup analysis further showed that cell-of-origin (COO) classification was an important factor affecting long-term survival in patients with R/R CNSL. Within the TP53+ group, patients with the non-germinal center B-cell-like (non-GCB) subtype had significantly longer overall survival than those with the GCB subtype (P=0.003).

The center's preliminary findings suggest that CAR-T cell therapy is an effective option for patients with TP53-mutated R/R CNSL and may be particularly beneficial for those with a non-GCB phenotype. These data may help clinicians when considering treatment strategies for this high-risk patient population.

Summary and Outlook

Prof. Xiaoyan Ke noted that the Department of Lymphoma and Myeloma at Beijing GoBroad Hospital has accumulated substantial experience with CAR-T therapy in recent years. As the number of real-world CAR-T cases continues to grow, the clinical questions encountered are becoming increasingly complex. Experience suggests that patients with TP53 mutations are often highly resistant to chemotherapy, while CAR-T therapy can still offer meaningful benefit. Identifying the right timing for CAR-T treatment and developing individualized, precise, end-to-end management strategies remain important priorities in hematologic oncology. Looking ahead, integrated assessment using clinical, pathological, molecular, and imaging data may help identify R/R CNSL patients who do not respond to conventional therapy but are more likely to benefit from precision CAR-T treatment. Monitoring approaches such as circulating tumor DNA (ctDNA) may also help detect signs of relapse earlier, allowing treatment to be initiated sooner and potentially extending survival.