Lymphoma is one of the fastest-growing malignant tumors worldwide, and the incidence rate in China has been gradually increasing in recent years, posing a serious threat to the health of the population. From January 26 to 28, 2024, the “Work Conference of the Leukemia Committee, Lymphoma Committee, and Myeloma Preparatory Committee of the Chinese Society of Clinical Oncology (CSCO) and the 2024 CSCO Academic Conference on Hematology, Lymphoma, and Myeloma Diseases” was successfully held in Haikou. Professor Huilai Zhang  from Tianjin Medical University Cancer Institute and Hospital shared insights at the conference on the survival status and diagnosis and treatment strategies for patients with indolent lymphoma, frontline treatment strategies for mantle cell lymphoma, and research progress on immunosuppressants. Following the conference, Oncology Frontier – Hematology Frontier invited Professor Zhang for an in-depth sharing session.

Oncology Frontier – Hematology Frontier：At the conference, you introduced the survival status and strategies for dealing with indolent lymphoma in China. Can you talk about the challenges China faces in diagnosing and treating indolent lymphoma and how to improve?

Professor Huilai Zhang : In this conference, I shared the current challenges and future directions for indolent lymphoma in China. Compared to aggressive lymphomas, patients with indolent lymphoma have a longer history of the disease and have their unique characteristics. For example, many patients feel very anxious when first diagnosed, requiring guidance from multidisciplinary teams and professional doctors, making patient education very important. Additionally, data show that nearly 23% of indolent lymphoma patients experience a long duration from onset to diagnosis, especially those who have not been further diagnosed by specialists. Therefore, precision medicine needs to be emphasized in future treatments; likewise, the accessibility of drugs and the implementation of innovative medications in health insurance have room for improvement.

Furthermore, indolent lymphoma requires full-course management by multidisciplinary professional teams. Full-course management is crucial for indolent lymphoma due to the long history of the disease, necessitating specialized teams. Recent research data from the United States indicate that lymphoma patients (including those with indolent lymphoma) treated by specialized or subspecialized teams have better overall survival. These findings set higher standards for the full-course management and specialization of lymphoma treatment in China. We look forward to specialized teams improving the survival of lymphoma patients in the future, especially for those with indolent lymphoma.

Oncology Frontier – Hematology Frontier：Currently, there are many unmet clinical needs in the treatment of Mantle Cell Lymphoma (MCL). At this conference, you presented an exciting report titled “Frontline Assault: New Breakthroughs in First-Line MCL Treatment.” Could you discuss how these new breakthroughs will change the current treatment landscape for MCL?

Professor Huilai Zhang : At the conference, I shared the progress in frontline treatment for MCL, including for younger patients in first-line therapy. The TRIANGLE study demonstrated that, compared to transplantation alone, the combination of BTK inhibitors and immunotherapy can significantly improve ORR and FFS. Therefore, in the era of BTK inhibitors and new drugs, some patients might achieve the same or even better efficacy with the first-line application of targeted drugs compared to transplantation. We are also looking forward to the TRIANGLE study results being equally effective in the real world in China.

For older patients, the application of drugs is even more critical than for younger patients, as these patients often cannot undergo transplantation schemes. At the recently concluded American Society of Hematology (ASH) annual meeting, our center also presented a single-arm, multicenter, prospective Phase 2 POLARIS study orally. By using ibrutinib combined with lenalidomide and rituximab as a first-line treatment for Mantle Cell Lymphoma, it was possible to achieve an overall ORR of 100%, with a CR rate close to 80%, and a high MRD-negative rate, while maintaining good safety. For patients whose clinical needs have not been met in the past, this study indicates that the strategy of advancing new drugs can bring new hope.

Oncology Frontier – Hematology Frontier：Lymphoma treatment has entered the era of immunotherapy. Could you discuss the recent advancements in the use of immune checkpoint inhibitors in lymphoma treatment, as well as the challenges that still exist?

Professor Huilai Zhang : I just shared at the conference the progress of immune checkpoint inhibitors in the treatment of lymphoma. In fact, in the past two years, there have been many new advancements in the field of treating lymphoma with immune checkpoint inhibitors. For classical Hodgkin lymphoma, moving PD-1 inhibitors to the frontline in combination with chemotherapy has shown good efficacy. Notably, a large Phase 3 study by the Southwest Oncology Group in the United States comparing PD-1 plus AVD versus BV plus AVD demonstrated promising prospects for PD-1 inhibitors as a frontline therapy. Additionally, the Sun Yat-sen University Cancer Center conducted a first-line treatment study on NK/T-cell lymphoma, finding that both PD-1 combined with anlotinib and pemetrexed sandwich radiotherapy, and PD-1 combined with P-Gemox, bring new hope and highlights.

Our center has also explored treatment for patients with bulky abdominal masses in follicular lymphoma. In the study, patients first received radiotherapy (18-24Gy), followed by PD-1 treatment and chemotherapy. The results showed that 5 out of 6 patients achieved CR, indicating that this treatment strategy is effective in reducing tumor burden and activating the immune system. Furthermore, we have explored combining PD-1 with other targeted drugs, including the JAK2 inhibitor ruxolitinib, the HDAC inhibitor chidamide, and gemcitabine, all of which are important research directions. Regarding the combination of PD-1 and CAR-T therapy, it has been observed that CAR-T cells may undergo a secondary expansion after PD-1 treatment, which also requires further exploration. Therefore, I believe the future will unveil new mechanisms of immune evasion in the field of PD-1, PD-L1, and other immunotherapies, and new combination treatment strategies will be explored. These are areas we are very focused on and see a promising future in.

Professor of Oncology, Chief Physician, Doctoral Supervisor. Currently serves as the Head of the Lymphoma Department at Tianjin Medical University Cancer Institute and Hospital. Main research areas: Molecular diagnosis and personalized treatment of malignant lymphoma. Vice Chairman of the Lymphoma Committee of the Chinese Anti-Cancer Association, Standing Committee Member of the Lymphoma Expert Committee of the Chinese Society of Clinical Oncology (CSCO), Member of the Lymphoma Group of the Oncology Branch of the Chinese Medical Association, Vice Chairman of the Oncology Branch of the China Health Promotion Foundation, Vice Chairman of the Lymphatic Diseases Committee of the Chinese Medical Education Association, Vice Chairman of the Lymphoma Committee of the China Association for the Advancement of Health Care in the Elderly, Chairman of the Oncology Clinical Chemotherapy Committee of the Tianjin Anti-Cancer Association, Deputy Director of the Tianjin Blood Disease Quality Control Center, Vice President of the Hematology Division of the Tianjin Medical Association. He has won one second prize and three third prizes of Tianjin Science and Technology Progress Award, and has presided over and participated in multiple projects funded by the National Natural Science Foundation of China and provincial-level scientific research projects. Currently, he serves as the Deputy Editor-in-Chief of “Journal of Oncology Pharmacy”, editorial board member of several domestic and international journals including “Chinese Journal of Hematology”, “Leukemia & Lymphoma”, “Chinese Clinical Oncology”, “Hematological Oncology”, “Blood Research”, “Discover Oncology”, and has published over seventy papers as the first author or corresponding author in international professional journals such as Blood, J Exp Med, JITC, Leukemia, CTM, AJH, BJH, Blood Adv, Front Oncol, Hematol Oncol, Int J Cancer, as well as in the Chinese journal series and national core journals. He has been awarded the fourth “National Famous Doctor · Outstanding Model” prize