From September 6-8, 2024, the 5th Tianjin International Lymphoma Symposium was successfully held. The conference featured twelve specialized sessions, including immunotherapy, translational research, and new drug development, creating a platform for promoting international academic exchange and collaboration. During the event, Hematology Frontier invited Dr. Hua Wang from the Sun Yat-sen University Cancer Center to review the latest treatment strategies for marginal zone lymphoma (MZL).01
Hematology Frontier: What new treatment strategies or drugs for MZL have shown significant efficacy in recent years? How would you evaluate their role in clinical practice?
Dr. Hua Wang: In recent years, there have been many advancements in MZL treatment, with the most notable being the increasing exploration of chemotherapy-free regimens. Current guidelines offer limited recommendations for chemotherapy-free options as first-line therapy, primarily focusing on the combination of lenalidomide and rituximab.
Significant progress has also been made in second-line and later treatments. Abroad, zanubrutinib has been approved for MZL, while in China, orelabrutinib has recently been approved for second-line and later treatment. The growing use of these small molecule targeted therapies in MZL reflects the high level of research activity in this field.
Additionally, Chinese researchers have initiated and participated in numerous prospective clinical trials combining rituximab with BTK inhibitors. In real-world practice, BTK inhibitors have also been used for relapsed/refractory patients or those with specific treatment needs as a first-line therapy, with encouraging results.
Emerging clinical research is also worth noting. Several ongoing registration trials aim to compare the efficacy and safety of BTK inhibitors combined with lenalidomide and rituximab (R2 regimen) against the traditional R2 regimen, as well as exploring the potential advantages of dual-antibody combinations over a single R2 regimen.
These therapeutic advancements are not only driving continuous optimization of MZL treatment strategies but also suggest that chemotherapy-free approaches may play a more prominent role in MZL treatment in the future, offering patients safer and more effective treatment options.
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Hematology Frontier: Regarding targeted therapy for MZL, such as BTK inhibitors and PI3K inhibitors, what role do they play in treatment? In your experience, what are the optimal timing and patient groups for using these drugs?
Dr. Hua Wang: In the current landscape of diverse treatment options, determining the optimal timing and patient selection has become a widely discussed topic in the medical community. Many MZL patients who receive first-line immunochemotherapy may still experience disease progression. Given that these patients are often older, with reduced willingness or tolerance for further chemotherapy, chemotherapy-free regimens become a preferred option. Such regimens have shown good complete response rates (CRR) and objective response rates (ORR) in clinical studies. For example, the response rate for orelabrutinib monotherapy exceeds 60%, and its efficacy may be further enhanced when combined with a CD20 monoclonal antibody. Therefore, BTK inhibitor treatment is suitable for these patients.
Additionally, special patient groups in first-line treatment, such as those with frailty or gastrointestinal involvement—who are at high risk for bowel obstruction and perforation—require careful selection of treatment plans. Extensive gastrointestinal involvement may limit surgical options and leave residual cancer after surgery, while systemic chemotherapy can lead to serious complications such as perforation or bleeding. In this context, a combination of BTK inhibitors and rituximab can gradually reduce tumor burden, decrease bowel infiltration, and shrink lesions, thus alleviating symptoms like constipation, abdominal pain, and obstruction severity.
Furthermore, for patients with bone marrow involvement but no significant organ involvement, the clinical presentation often includes thrombocytopenia and anemia. For elderly patients with poor tolerance, immunochemotherapy may exacerbate bone marrow suppression, leading to increased long-term hospitalization and transfusion support. In contrast, a treatment strategy led by BTK inhibitors can rapidly reduce tumor burden, often showing improvements in blood cell counts within one to two weeks.
As for PI3K inhibitors, their efficacy is recognized, but the toxicity risks have limited their widespread clinical use. Although approved for indications abroad, their approval has been withdrawn due to significant toxicity concerns, and they are not yet approved in China.
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Hematology Frontier: Is there a trend toward using BTK inhibitors in combination with other therapies, such as immunotherapy or chemotherapy, for MZL treatment? What is the potential of these combination therapies in improving efficacy and reducing relapse rates?
Dr. Hua Wang: When discussing combination strategies with BTK inhibitors, their combination with CD20 monoclonal antibodies is a promising two-drug option. To further enhance efficacy, lenalidomide could be added to form a three-drug regimen, potentially increasing the CRR. However, for patients with a relatively low tumor burden, a three-drug regimen may not be necessary.
For high-risk patients, especially those with an International Prognostic Index (IPI) score above three or large tumor burden, multi-drug combination therapies are more appropriate. Additionally, combining BTK inhibitors with traditional immunochemotherapy regimens (such as R-CHOP or BR) is an avenue worth exploring.
To optimize treatment strategies for MZL in the future, more clinical studies could be conducted to evaluate the synergistic effects of BTK inhibitors added to traditional immunochemotherapy, thus providing patients with more precise and effective treatment options.
Dr. Hua Wang:
Associate Chief Physician, Master’s Supervisor, PhD in Clinical Oncology, Sun Yat-sen University Cancer Center Committee Member, Tumor and Microecology Committee, Chinese Anti-Cancer Association Youth Vice Chair, Chronic Lymphocytic Leukemia Working Group, China Standing Committee Member, Cell Therapy Committee, China Health Promotion and Technology Association Committee Member, Plasma Cell Disease Committee, China Health Promotion and Technology Association Standing Committee Member, Hematology Committee, Guangdong Medical Education Association Council Member, Guangzhou Anti-Cancer Association, and Standing Committee Member, Tumor Recurrence and Metastasis Committee
Specializes in the precise diagnosis and personalized treatment of myeloma and lymphoma, with extensive experience in new drug research for myeloma. Has published over 40 SCI papers in journals such as Molecular Cancer, Leukemia, JHO, BJC, Oncologist, and CMJ as the first or corresponding author. Leads several research projects funded by the National Natural Science Foundation and the Guangdong Natural Science Foundation.
