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 treatment is ineffective or those who relapse after a brief period of effectiveness. Beyond exploring factors that may affect the efficacy of CD19 CAR-T therapy, many doctors and researchers are actively seeking effective treatments for these patients. In June this year, Dr. Xiaoyan Ke and Dr. Kai Hu's team from Beijing GoBroad Boren Hospital published an article titled “Salvage CD20-SD-CART therapy in aggressive B-cell lymphoma after CD19 CART treatment failure” in the Frontiers in Oncology, providing new insights into treatment options for B-cell lymphoma patients who have failed CD19 CAR-T therapy. 

Research Highlights

1. Sequential CD20 CAR-T Therapy Post-CD19 CAR-T Failure Shows Higher Efficacy Than Salvage Chemotherapy and Significantly Prolongs Survival

Dr.  Kai Hu pointed out the innovation in this study: currently, international researchers focus on new drug-inclusive chemotherapy, 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 sequential CAR-T therapy with a different target. Our team summarized the treatment results of 93 B-cell lymphoma patients who failed CD19 CAR-T therapy at our center to find more effective treatment options. Among the 93 patients, 54 (58%) chose sequential CD20-targeted CAR-T therapy, while 39 (42%) opted for chemotherapy combined with new drugs and targeted therapies. Results showed that the complete response rate (CRR) in the sequential CD20 CAR-T group was significantly higher than in the chemotherapy group (27.8% vs. 7.9%, P=0.03). After a median follow-up of 18.54 months, the sequential CD20 CAR-T group significantly extended both 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 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).

2. Sequential CD20 CAR-T Therapy is Safe and Controllable

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

3. What Factors Affect the Efficacy of Sequential CAR-T Therapy?

Using a univariate regression model, we assessed factors affecting the response to sequential CD20-targeted CAR-T therapy. We found that an IPI score ≥3 (OR 0.3, 95% CI: 0.10-0.93, P=0.04) was significantly associated with a reduced overall response rate (ORR). Additionally, ECOG PS ≥3 (HR 3.12, 95% CI: 1.23-7.94, P=0.02) was associated with reduced progression-free survival and overall survival.

Research Commentary

Dr.  Xiaoyan Ke noted that the Lymphoma and Myeloma Department at Beijing GoBroad Hospital has accumulated extensive experience with CAR-T therapy in recent years. With the increasing number of real-world cases, CD19 CAR-T may cure about half of the patients with relapsed/refractory B-cell lymphoma. For patients who fail CD19 CAR-T therapy, clinical challenges become more complex. Our experience suggests that selecting a different target, such as CD20, for second-line CAR-T therapy based on the expression of recurrent tumor surface antigens can achieve better efficacy than salvage chemotherapy, extend patient survival, and ensure controllable safety. Tumor burden and the patient’s physical condition remain factors influencing the efficacy of sequential CD20 CAR-T therapy.

Xiaoyan Ke

Chief Physician, MD, Chief Physician at Peking University Third Hospital, Leader of the Adult Lymphoma Program at Beijing GoBroad Medical (Hematology) Beijing Research Center, PhD Supervisor, Second-level Dr. , and Chief Consultant at the Lymphoma and Myeloma Department at Beijing GoBroad Hospital, Beijing GoBroad Medical (Hematology) Beijing Research Center.

Academic Positions:

• Former Chair of the Hematology Society of the Chinese Women Physicians Association
• Chair of the Targeted Therapy Professional Committee of the Chinese Women Physicians Association
• Executive Deputy Chair of the Oncology Expert Committee of the Chinese Women Physicians Association
• Vice Chair of the Hematology Tumor Committee of the Chinese Geriatric Society
• Vice Chair of the Hematology Professional Committee of the Chinese Medical Education Association
• Standing Member of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association
• Deputy Editor of the Journal of Leukemia and Lymphoma and editorial board member of several journals
• Medical technology appraisal consultant for the Ministry of Health and Beijing
• Central health consultation expert

Kai Hu

Chief Physician, MD, Director of the Lymphoma and Myeloma Department at Beijing GoBroad Hospital.

Dr. Hu earned his bachelor’s degree in Clinical Medicine from West China Medical University (1997-2002), a master’s degree in Internal Medicine from Sichuan University West China Medical Center (2002-2005), and a doctorate in Clinical Internal Medicine (Hematology) from Peking University Health Science Center (2009-2012). He has served as an attending physician and later an associate chief physician at Peking University Third Hospital. From 2019 to February 2024, he served as the administrative director of the Adult Lymphoma Department at Beijing GoBroad Borin Hospital. Since March 2024, he has been the administrative director of the Lymphoma and Myeloma Department at Beijing GoBroad Hospital.

With nearly 20 years of experience in hematology, Dr. Hu specializes in the standardized diagnosis and treatment of hematologic malignancies such as leukemia, lymphoma, and multiple myeloma, as well as immunotherapy (CAR-T cell therapy, CIK/NK cell immunotherapy). He is proficient in comprehensive standardized treatment primarily based on internal chemotherapy, molecular targeted therapy, autologous/allogeneic hematopoietic stem cell transplantation, and biological therapy. Dr. Hu has pioneered exploratory studies on CAR-T therapy for central nervous system lymphoma, myeloma, and post-CD19 CAR-T failure treatments, as well as the novel model of combining allogeneic CAR-T with allogeneic hematopoietic stem cell transplantation for lymphoma and myeloma in China. He has performed nearly 1000 CAR-T treatments and participated in nearly 40 clinical trials as a principal investigator and over 100 as a co-investigator. He has authored or co-authored over 40 papers in Chinese and English and contributed to five books. Dr. Hu has presented his team’s research findings at domestic and international academic conferences, including the American Society of Hematology Annual Meeting and the European Hematology Association Annual Meeting.

Academic Positions:

• Chair of the Precision Diagnosis and Treatment Professional Committee for Hematologic Oncology at the Beijing Health Promotion Association
• Executive Committee Member of the Lymphoma Immunotherapy Professional Committee at the Beijing Cancer Prevention and Treatment Society
• Member of the Geriatric Oncology Professional Committee at the Chinese Society of Geriatrics
• Member of the Health Science Popularization Professional Committee at the Chinese Health Management Association
• Member of the Oncology Professional Committee at the Beijing Association of Integrative Medicine
• Member of the Hematopoietic Stem Cell Transplantation and Cell Therapy Professional Committee at the Chinese Medical Education Association
• Member of the T-cell Lymphoma Working Group at the Hematologic Oncology Professional Committee at the Chinese Anti-Cancer Association
• Member of the Hematology Professional Committee at the Beijing Perioperative Medicine Research Association
• Member of the Expert Committee for “Hub-type” Social Organizations at the Beijing Society
• Youth Committee Member of the Hematology Committee at the Beijing Medical Association
• Member of the Hematopoietic Stem Cell Transplantation and Cell Therapy Professional Committee at the Chinese Medical Education Association
• Member of the Clinical Research Professional Committee at the Beijing Oncology Society

References: Fei Xue, Peihao Zheng, et al. Salvage CD20-SD-CART therapy in aggressive B-cell lymphoma after CD19 CART treatment failure. Front. Oncol. 14:1376490. DOI: 10.3389/fonc.2024.1376490.