Editor's Note: As the efficacy of CAR-T therapy in B-cell lymphoma becomes increasingly recognized, some studies have focused on its application in treating refractory/relapsed central nervous system (CNS) B-cell lymphoma. Refractory/relapsed CNS B-cell lymphoma patients were initially excluded from early CAR-T clinical trials, but as CAR-T therapy's real-world application grows, these patients can achieve optimistic outcomes. However, patients with high tumor burden face a high incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) and poor outcomes. There is an urgent need for an effective bridging therapy to reduce ICANS incidence and improve remission rates in multidrug-resistant CNS-involved patients. From June 13-16, 2024, at the 29th European Hematology Association (EHA) Annual Meeting, Dr. Hui Shi from Professors Xiaoyan Ke and Kai Hu's team at Beijing Gaobo Hospital will present a report titled "INCORPORATING RADIATION WITH CAR T-CELL THERAPY DEMONSTRATED A HIGH RATE OF REMISSION IN PATIENTS WITH B CELL LYMPHOMA INVOLVING THE CNS," offering new insights for treating refractory/relapsed multidrug-resistant CNS B-cell lymphoma patients.Research Highlights – Breaking Barriers, Excellent Efficacy
Professor Kai Hu noted that to reduce treatment-related mortality and improve efficacy in CAR-T cell therapy for refractory/relapsed CNS B-cell lymphoma, the search for an “effective CAR-T bridging therapy” has been challenging, but there is hope for breakthroughs.
We retrospectively analyzed the safety and efficacy of combining radiotherapy with CAR-T cell therapy in patients with CNS-involved B-cell lymphoma. A total of 13 patients were included in this study. All patients showed resistance to MTX, Thiotepa, Ara-C, and BTK inhibitors. The cohort included secondary CNS involvement, such as 2 cases of DLBCL, 1 case of FL, 1 case of PMBL, 1 case of Burkitt, and 1 case of Richter’s transformation, as well as 7 cases of primary CNS lymphomas (PCNSLs). All patients received whole-brain radiotherapy before CAR-T treatment, with some receiving additional localized boost radiotherapy. After radiotherapy, patients began lymphodepletion and CAR-T cell infusion.
The overall CR rate after treatment was 84.6%, with a CR maintenance rate of 61.5%. The median overall survival (OS) and progression-free survival (PFS) were 224 days and 163 days, respectively. CRS occurred in 53.8% of patients, with all cases being grade 1 except for one patient who developed grade 4 ICANS and died of disease progression. Combining radiotherapy with CAR-T cell therapy showed good survival rates and tolerance in CNS-involved B-cell lymphoma patients, reducing ICANS incidence.
This approach offers a viable strategy for treating patients with multidrug-resistant CNS involvement.
Summary and Outlook
Professor Xiaoyan Ke mentioned that the initial study results show that salvage therapy with whole-brain radiotherapy before CAR-T treatment for refractory/relapsed CNS B-cell lymphoma patients achieves good survival rates and is well tolerated. It may be a viable bridging therapy option before CAR-T treatment for these patients. However, the risk of ICANS during treatment remains a significant concern.
Based on the initial results, we have conducted further clinical observations and studies, hoping to find more suitable and effective treatment methods through continuous exploration to save more patients and help them regain health and embrace a new life.
