From November 14 to 17, 2024, the Cellular Therapy and Immunotherapy (CTI) Conference was held in Hangzhou, China, bringing together leading global experts, scholars, and industry leaders in the field of cell and immunotherapy. This conference served not only as a platform for academic exchange but also as a vital window to showcase cutting-edge research and drive advancements in the field. Dr. Peihua Lu, a pioneer in CAR-T clinical trials and a leader at Beijing Lu Daopei Hospital, shared groundbreaking progress on CAR-T therapies for T-cell malignancies at CTI 2024, following earlier presentations on CD7 CAR-T therapy for T-ALL/LBL at The twelfth annual meeting of the Society of Hematologic Oncology (SOHO 2024)  meeting. In an exclusive interview with Hematology Frontier, Professor Lu discussed strategies for applying CAR-T therapy across different types and stages of T-cell malignancies, China’s role in global CAR-T research, and the importance of international collaboration.

Q1: How do CAR-T therapy application strategies vary across different types and stages of T-cell malignancies? What are the key differences?

Dr. Peihua Lu: Since 2015, our team has been dedicated to CAR-T cell therapy research and has established close collaborations with companies specializing in CAR-T product development. Through these partnerships, we have gained extensive experience in target selection, treatment planning, and managing adverse effects. While CAR-T therapy for B-cell malignancies has achieved notable success, with some commercially available products, T-cell malignancies remain in the relatively early stages of clinical exploration.

T-cell malignancies encompass diverse subtypes. Although some can be treated with shared CAR-T targets, therapeutic outcomes vary significantly among different types. Our research has focused on addressing the unmet clinical needs of patients with relapsed or refractory T-cell malignancies. For instance, CAR-T therapy has demonstrated encouraging efficacy in T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), even for heavily pretreated patients. These findings were highlighted in our presentation at SOHO 2024. However, achieving sustained remission and long-term cures remains our ultimate goal.

To this end, we have integrated CAR-T therapy with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Long-term follow-up over three to four years has shown that this combined approach outperforms standalone treatments.

Additionally, we are exploring CD7 CAR-T therapy combined with allo-HSCT for acute myeloid leukemia (AML), yielding promising preliminary results soon to be published in Blood. We have also applied CD7 CAR-T therapy to peripheral T-cell lymphoma (PTCL) cases, achieving positive outcomes despite limited patient numbers. Differences in therapeutic outcomes across T-cell malignancy subtypes, such as dosage selection, bridging chemotherapy, and preconditioning regimens, are areas we are continuously refining. Importantly, we have observed potential for complete remission in some relapsed or refractory patients.

Our team remains committed to optimizing CAR-T therapy for diverse T-cell malignancies, aiming to deliver improved therapeutic outcomes and enhance patients’ quality of life.

Q2: Chinese CAR-T research has garnered international attention. How would you evaluate China’s position in global CAR-T research, and what role does international collaboration play in advancing this field?

Dr. Peihua Lu: Over the years, our team has presented numerous CAR-T research findings at international conferences, earning widespread recognition from the global hematology community. We emphasize integrating academic research with clinical practice and actively engage with domestic and international experts to explore safe and effective treatments for hematologic malignancies.

China stands at the forefront of global CAR-T research, excelling in both the number of clinical trials and the efficiency of new product development. While competition fosters innovation, collaboration allows us to pool resources, knowledge, and expertise, expediting the development of CAR-T therapies. This synergy drives clinical progress and facilitates groundbreaking advancements.

Moreover, international collaboration enhances our understanding of patient-specific variations, enabling the development of more precise and effective treatment strategies. Our ultimate goal is to produce high-quality CAR-T products for global use. Such collaborations not only expand the accessibility of CAR-T therapies but also reflect our commitment to serving the global patient community.

China’s researchers and clinical trial teams have achieved significant milestones through close cooperation and alignment with international standards. These accomplishments have attracted numerous international collaboration opportunities, with many academic organizations and hospitals expressing interest in partnering with China. We are enthusiastic about fostering these collaborations to propel CAR-T research and application to new heights.

Q3: What are the future research directions and challenges for CAR-T therapy in treating T-cell malignancies? What plans does your team have for addressing these issues?

Dr. Peihua Lu: While CD7 CAR-T therapy has shown promise for T-cell malignancies, we face several challenges, including enhancing the specificity of CAR-T cells to minimize off-target effects and managing the toxicity associated with therapy, such as cytokine release syndrome (CRS) and neurotoxicity observed in CD19 CAR-T treatments.

To address these challenges, our research focuses on several key areas. First, we aim to optimize CAR-T products by enhancing their specificity and safety. For example, we have advanced CAR-T technology to include nanobody-based CAR-T cells, which have already shown success in clinical applications. Second, we are exploring new targets, including dual-target CAR-T therapies for T-cell malignancies. By pursuing these innovative approaches, we hope to overcome existing challenges and provide safer, more effective treatment options.

We remain confident in our ability to tackle these obstacles and are motivated by the trust patients place in our team. This trust is vital to the progress of our clinical trials. We look forward to achieving further breakthroughs and expanding the range of treatment options available to patients.

Dr. Peihua Lu

Executive Director of Medical Services at Lu Daopei Hospital Director of the Beijing Lu Daopei Institute of Hematology

Dr. Peihua Lu graduated from Peking University Medical School and completed her residency at the University of Nebraska Medical Center. She later specialized in hematology and oncology at Stanford University. She is a certified hematologist and oncologist in the United States and holds medical licenses in both China and the United States.

Her roles include:

• Executive Committee Member, Cancer Research Center, Capital Medical University
• Executive Director, Blood Disease Committee, China Non-Governmental Medical Institutions Association
• Member, Hematopoietic Stem Cell Donor Registry of China
• Executive Committee Member, Leukemia Alliance, Chinese Society of Clinical Oncology (CSCO)
• Recipient of the Medical Management Award, Taishan Healthcare Value Award, 2021