Professor Lei Fan: Internal Medicine Treatment and Research Progress of Ocular Lymphoma | First Academic Forum of the Ocular Lymphoma Collaboration Group

On March 30, 2024, the First Academic Forum of the Ocular Lymphoma Collaboration Group was successfully held in Beijing. It was hosted by Beijing Tongren Hospital affiliated with Capital Medical University, China Human Health Technology Promotion Association, Beijing Public Health Science Popularization Promotion Association, and Beijing Chen Jumei Charity Foundation. The event was organized by the Cell Immunotherapy Committee of the China Human Health Technology Promotion Association. Renowned experts and scholars from both domestic and international communities actively exchanged ideas and engaged in discussions about the latest advancements and hot topics in the diagnosis and treatment of ocular lymphoma. Professor Lei Fan from Jiangsu Provincial People’s Hospital was specially invited by “Oncology Frontier – Hematology Frontier” to share updates in the research on improving prognosis, novel biomarkers, and prevention of recurrence in the internal medicine treatment of ocular lymphoma.

“Oncology Frontier – Hematology Frontier”: What are the unresolved key issues in the field of internal medicine treatment of ocular lymphoma? How do you think solving these problems could impact treatment outcomes and patient prognosis?

Professor Lei Fan: Ocular lymphoma is defined by its organ-specific occurrence, referring to lymphomas that develop in and around the eyes and their appendages. Generally, ocular lymphomas are categorized into two types: aggressive lymphomas and indolent lymphomas. Indolent lymphomas, which are low-grade malignancies, often affect the adnexa of the eye rather than the eye itself. The most common indolent lymphoma is Mucosa-Associated Lymphoid Tissue (MALT) lymphoma. Aggressive lymphomas, mostly Diffuse Large B-Cell Lymphoma (DLBCL) with a few cases of T-cell and Burkitt lymphoma, often invade the eyeball or optic nerve, typically resulting in poor prognosis. The location of the lesions makes previous treatments less than ideal.

The unmet clinical needs of these two types of lymphomas differ. The overall prognosis for ocular adnexal MALT lymphoma is generally good. Clinicians focus on minimizing treatment, such as using only surgery or a combination of surgery, radiotherapy, or targeted therapy, to control the disease while reducing side effects. Such patients should ideally avoid chemotherapy. Our center (Jiangsu Provincial People’s Hospital) has explored the use of targeted drugs like rituximab combined with local low-dose radiotherapy for limited-stage MALT lymphoma, including ocular MALT lymphoma, achieving good long-term disease control. The overall prognosis for aggressive lymphomas remains poor, with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy not offering very optimistic outcomes, thus necessitating exploration of new treatment approaches to improve clinical prognosis.

“Oncology Frontier – Hematology Frontier“: In the research on internal medicine treatment of ocular lymphoma, what new biomarkers have been discovered? What potential applications do these biomarkers have?

Professor Lei Fan: Biomarkers are predominantly focused on aggressive lymphomas in the eye, particularly Diffuse Large B-Cell Lymphoma of the primary vitreoretinal type (PVRLBCL). These diseases, located in the eye, often result in insufficient diagnostic tissue from surgeries, leading to potential underdiagnoses or misdiagnoses.

Recent advancements include additional biomarkers to traditional pathology for primary vitreoretinal large B-cell lymphoma, such as the IL6/IL10 ratio, MYD88 mutations, and clonality of IGH gene rearrangements. These novel biomarkers, combined with traditional cytology, have significantly increased diagnostic success rates, reducing underdiagnoses and misdiagnoses, thus enabling more precise diagnostics. These molecular markers are valuable not only in diagnostics and differential diagnostics but also guide subsequent clinical treatments. For example, the presence of MYD88 mutations, usually in the MCD type of diffuse large B-cell lymphoma, suggests the addition of BTK inhibitors to the treatment regimen, further improving efficacy and survival rates.

“Oncology Frontier – Hematology Frontier“: Recurrence of ocular lymphoma remains a challenging aspect of treatment. What research directions do you think are worth focusing on and investing in to prevent recurrence of ocular lymphoma in the future?

Professor Lei Fan: The issue of ocular lymphoma recurrence is divided into two parts. The first part concerns ocular adnexal MALT lymphoma, where surgical treatment alone may leave residual disease, leading to progression. The current strategy involves multiple treatment methods combined, such as targeted drugs like rituximab with surgery or radiotherapy. The advantage of combined treatment is better disease control without significantly increasing treatment-related side effects, thus significantly reducing the rate of recurrence.

The second part concerns aggressive ocular large B-cell lymphomas, which traditionally use the R-CHOP regimen. As clinicians deepen their understanding of these diseases, they increasingly recognize these biological characteristics as similar to primary central nervous system large B-cell lymphomas, leading to the use of rituximab combined with high-dose methotrexate. Furthermore, based on tumor biology features like MYD88 mutations, combining new BTK inhibitors can significantly improve treatment effects and reduce the likelihood of recurrence, thereby enhancing clinical efficacy and prognosis for patients.