Chinese Medical Team: Sequential CD20 CAR-T Therapy Outperforms Salvage Chemotherapy for CD19 CAR-T Resistant B-Cell Lymphoma Patients

## Chinese Medical Team: Sequential CD20 CAR-T Therapy Outperforms Salvage Chemotherapy for CD19 CAR-T Resistant B-Cell Lymphoma Patients

CAR-T therapy

In recent years, with the application of CD19 CAR-T in refractory/relapsed B-cell lymphoma, we have encountered patients for whom CD19 CAR-T therapy was ineffective or who relapsed shortly after initial success. While research continues to explore factors that may affect the efficacy of CD19 CAR-T therapy, doctors and scholars are actively seeking more effective treatments for these patients. In June of this year, Professor Ke Xiaoyan and Professor Hu Kai from the Lymphoma and Myeloma Department of Beijing Gaobo Hospital published an article titled “Salvage CD20-SD-CART Therapy in Aggressive B-Cell Lymphoma After CD19 CART Treatment Failure” in the journal *Frontiers in Oncology*. This study provides new insights for treating B-cell lymphoma patients who have failed CD19 CAR-T therapy.

### Efficacy of Sequential CD20 CAR-T Therapy Exceeds Salvage Chemotherapy Post-CD19 CAR-T Failure

Regarding the innovation of this research, Professor Hu Kai pointed out that international scholars currently focus on chemotherapy (including new drugs), targeted drug therapy, and allogeneic hematopoietic stem cell transplantation for B-cell lymphoma patients who have failed CD19 CAR-T therapy. However, there is limited data on switching targets for a second CAR-T therapy. Our team summarized the treatment outcomes of 93 B-cell lymphoma patients who failed CD19 CAR-T therapy. Among them, 54 out of 93 (58%) chose sequential CD20-targeted second CAR-T therapy, and 39 out of 93 (42%) opted for chemotherapy combined with new drugs and targeted therapy. The results showed that the complete remission rate (CRR) in the sequential CD20 CAR-T group was significantly higher than in the chemotherapy group, with rates of 27.8% and 7.9%, respectively (P=0.03).

After a median follow-up period of 18.54 months, the sequential CD20 CAR-T group showed a significantly longer median progression-free survival (4.04 months vs. 2.27 months, P=0.0032) and median overall survival (8.15 months vs. 3.02 months, P<0.0001) compared to the non-CAR-T group. Multivariate analysis further confirmed that sequential CD20-targeted second CAR-T therapy is an independent factor associated with improved overall survival (HR 0.28, 95%CI: 0.16-0.51; P<0.0001) and progression-free survival (HR 0.46, 95%CI: 0.27-0.8; P=0.005).

### Safety of Sequential CD20-Targeted Second CAR-T Therapy

The study noted that the incidence of severe CRS (≥ grade 3) and ICANS (≥ grade 3) was relatively low during the sequential CD20-targeted second CAR-T therapy, at 9.2% and 7.4%, respectively, with complete recovery after treatment. Other adverse reactions were also controllable.

### Factors Affecting the Efficacy of Second CAR-T Therapy

We used a univariate regression model to evaluate factors affecting the response to sequential CD20-targeted second CAR-T therapy. An IPI score of ≥3 (OR 0.3, 95%CI: 0.10-0.93, P=0.04) was significantly associated with a lower overall response rate (ORR). Additionally, ECOG PS ≥3 (HR 3.12, 95%CI: 1.23-7.94, P=0.02) was associated with decreased progression-free survival and overall survival.

### Study Commentary

Professor Ke Xiaoyan highlighted that the Lymphoma and Myeloma Department at Beijing Gaobo Hospital has accumulated extensive experience with CAR-T therapy in recent years. As the number of CAR-T cases increases in real-world scenarios, CD19 CAR-T may cure half of the patients with relapsed/refractory B-cell lymphoma. For patients who fail CD19 CAR-T therapy, clinical problems become more complex. Our experience suggests that selecting CD20-targeted second CAR-T therapy based on the expression of surface antigens on recurrent tumors can still achieve better results than salvage chemotherapy, extend patient survival, and maintain controllable safety. Tumor burden and the patient’s physical condition remain factors affecting the efficacy of sequential CD20 CAR-T therapy.

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