On July 20, 2024, the 5th Lymphoma & Myeloma Immunotherapy and Targeted Therapy Conference, along with the Gaobo Medical Academic Conference, was successfully held in Beijing. With the core concepts of "Precision, Integration, Innovation," the conference closely followed the latest developments and frontier topics from the 29th European Hematology Association (EHA 2024) and the 2024 American Society of Clinical Oncology (ASCO) annual meetings. At this conference, Dr. Lin Fu from the Department of Hematology at Beijing Tiantan Hospital delivered an insightful presentation on the "Advances in Diagnosis and Treatment of Primary Central Nervous System Lymphoma (PCNSL)." To capture the conference's dynamics and facilitate in-depth exchange, Oncology Frontier - Hematology Frontier conducted an exclusive interview with Dr. Lin Fu. The following is a summary for readers' reference.Oncology Frontier – Hematology Frontier: In the induction treatment of primary central nervous system lymphoma (PCNSL), HD-MTX-based combination chemotherapy is the first-line choice. However, there is still controversy regarding the combination with CD20 monoclonal antibody rituximab. Could you share your views on this issue?
Dr. Lin Fu: Unlike peripheral lymphomas, the treatment drugs for PCNSL need to cross the blood-brain barrier (BBB) to be effective. As a large molecule drug, CD20 monoclonal antibody cannot cross the BBB, which raises some controversy over its use in PCNSL treatment. Two previous randomized controlled trials (RCTs) have demonstrated that adding CD20 monoclonal antibody to PCNSL treatment does not bring additional benefits. However, it should be noted that PCNSL patients often have early disruption of the BBB due to the presence of tumor lesions, allowing CD20 monoclonal antibody to exert some therapeutic effects in the early stages of PCNSL. Therefore, it can be applied clinically.
Oncology Frontier – Hematology Frontier: Given the good efficacy of new drugs such as BTK inhibitors (BTKi) and immunomodulatory drugs (IMiDs) in relapsed/refractory PCNSL, many experts in the field have attempted to move these new drugs to first-line combination regimens. Early research results are also encouraging. Could you introduce the research progress in this area?
Dr. Lin Fu: PCNSL is an aggressive hematologic malignancy highly sensitive to chemotherapy, achieving significant remission rates post-chemotherapy but also prone to relapse. The current treatment regimen for PCNSL is still based on high-dose methotrexate (HD-MTX). However, recent studies have shown that the B-cell receptor (BCR) pathway plays a crucial role in the treatment of B-cell lymphomas, and the application of BTK inhibitors (BTKi) has achieved good results in PCNSL treatment. Immunomodulatory drugs (IMiDs) also have proven efficacy in PCNSL. It is important to note that BTKi and IMiDs (such as lenalidomide/pomalidomide) can partially cross the BBB, thus playing a significant role in PCNSL treatment. The current viewpoint suggests that combining chemotherapy with BTKi or lenalidomide can yield good results in PCNSL. However, since there is no standard induction chemotherapy regimen for PCNSL, the application of BTKi or lenalidomide is mostly concentrated in single-arm prospective clinical studies. The optimal induction treatment regimen for PCNSL is still undetermined and requires further exploration. The combination of BTKi or lenalidomide with chemotherapy is becoming increasingly valuable in first-line PCNSL treatment, crucial for the overall benefit of PCNSL patients.
Oncology Frontier – Hematology Frontier: Given the recurrent nature of PCNSL, maintenance therapy is currently recommended. Maintenance drugs include lenalidomide, BTK inhibitors combined with HD-MTX, and temozolomide. Could you comment on how to choose maintenance therapy for PCNSL based on relevant research data?
Dr. Lin Fu: Indeed, PCNSL is a type of lymphoma that is prone to remission and relapse. The current induction treatment is based on high-dose methotrexate (MTX), and post-induction therapy requires consolidation treatment, which mainly includes three options: autologous stem cell transplantation (ASCT), radiotherapy (RT), and non-myeloablative chemotherapy. All have clinical applications and their own focuses. After consolidation therapy, the role of maintenance therapy cannot be overlooked. Due to the BBB, the drugs that can effectively cross it in frontline treatment are relatively limited. Therefore, the current consensus recommends maintenance therapy for PCNSL. In terms of maintenance therapy options, if the drug dosage was relatively sufficient during frontline treatment, single-agent maintenance therapy (choosing one among lenalidomide, BTKi, or temozolomide) can be applied. If the dosage was insufficient or the patient did not reach the desired remission status, two drugs among lenalidomide, BTKi, or temozolomide can be selected for maintenance therapy.
Dr. Lin Fu
- Director of the Department of Hematology, Beijing Tiantan Hospital, Capital Medical University
- Chief Physician, Doctoral Supervisor
- Standing Committee Member of the Youth Committee of the Hematology Professional Committee, China Medical Education Association
- Member of the Precision Diagnosis and Treatment Professional Committee for Hematologic Diseases, China Research Hospital Association
- Member of the Hematology Branch, Chinese Society of Gerontology and Geriatrics
- Recognized as a Famous Doctor in Lingnan and a Good Doctor in Yangcheng
- Review expert for the National Natural Science Foundation of China
- Deputy Editor of the Journal of Thrombosis and Hemostasis
