From September 25 to September 29, the 27th National Clinical Oncology Conference and CSCO Annual Meeting, organized by the Chinese Society of Clinical Oncology (CSCO) and the Beijing Xisike Clinical Oncology Research Foundation, was successfully held in Xiamen. During the conference, Hematology Frontier invited Dr. Zhiming Li from Sun Yat-sen University Cancer Center to share his strategies for treating diffuse large B-cell lymphoma (DLBCL).

First-Line Treatment for Newly Diagnosed DLBCL Patients

Hematology Frontier: In your view, what are the recommended first-line treatment options for newly diagnosed DLBCL patients? What key factors should be considered when selecting an initial treatment plan to improve the cure rate and quality of life?

Dr. Zhiming Li: DLBCL is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for 30% to 40% of new NHL cases globally. Despite standard first-line treatment with the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), around 40% of patients experience relapsed or refractory disease. The POLARIX study demonstrated that the Pola-R-CHP regimen (which replaces vincristine with polatuzumab vedotin) significantly reduced the risk of disease progression by 36% in Asian populations over two years and achieved deeper molecular remission compared to R-CHOP. The latest CSCO guidelines have included Pola-R-CHP as a Grade I-A recommendation for newly diagnosed DLBCL patients. Therefore, Pola-R-CHP should be the preferred first-line treatment option where accessible.

When initiating DLBCL treatment, a comprehensive evaluation of the patient’s age, physical condition, clinical staging, pathological type, molecular and genetic characteristics, and interim PET/CT assessment should guide the treatment strategy. High-risk patients with extranodal involvement should receive more aggressive treatments like Pola-R-CHP, even if their IPI score indicates low risk. For patients who do not achieve a complete response (CR) at interim PET/CT, the addition of “X” drugs can be considered if their physical condition permits. Additionally, for patients aged 60 to 80 who tolerate toxicity well, maintenance with lenalidomide can further improve prognosis.

New Treatment Strategies for Relapsed or Refractory DLBCL

Hematology Frontier: With the development of immunotherapy and targeted therapies, what new treatment strategies have been incorporated into clinical practice for relapsed or refractory DLBCL? How should these new therapies be integrated with traditional treatments?

Dr. Zhiming Li: Despite progress in first-line treatment for DLBCL, 30% to 40% of patients experience disease progression during or after initial treatment (defined as primary refractory) or relapse after an initial response. For transplant-eligible patients who experience their first relapse, the standard second-line treatment involves salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, two major challenges persist: first, ASCT can offer a cure, but patients with primary refractory disease or early relapse (within one year of initial diagnosis) often have poor ASCT success rates and very poor prognoses. Second, studies have shown that achieving CR before transplantation is critical for long-term survival, but the CR rate with salvage chemotherapy alone is often below 40%, highlighting the need for more effective treatments.

For third-line and beyond relapsed/refractory (R/R) DLBCL patients, treatment options are extremely limited, involving allogeneic stem cell transplantation (allo-SCT), clinical trials, or CAR-T therapy as rescue treatments. There is an urgent need for new targeted and immunotherapeutic drugs to improve clinical outcomes for relapsed/refractory patients.

Recent advancements include targeted drugs such as the CD79b ADC polatuzumab vedotin, CD20×CD3 bispecific antibodies (glofitamab, epcoritamab), and CAR-T therapies, all of which have shown clear advantages over traditional treatments in increasing response rates and prolonging patient survival. The Pola-BR regimen and glofitamab have been approved by the NMPA for treating adult R/R DLBCL patients who are ineligible for transplantation and have received at least two prior lines of systemic therapy. They have also been included in the CSCO lymphoma guidelines.

Additionally, the STARGLO study presented at the 2024 EHA meeting revealed that Glofit-GemOx reduced the risk of death by 41% compared to R-GemOx in R/R DLBCL patients, with good safety. This is the first head-to-head phase III randomized controlled trial to achieve a positive OS outcome in transplant-ineligible R/R DLBCL patients, offering new hope for clinical cure.

Looking ahead, advancing targeted therapies and T-cell therapies from later lines to earlier lines to benefit patients sooner and reduce the risk of recurrence remains a priority. Combination regimens of new drugs are crucial for achieving clinical cures. For patients who are refractory to first-line chemotherapy or progress after Pola-R-CHP, targeted CD79b ADCs, bispecific antibodies, and CAR-T cell therapies should be considered as preferred options in second-line treatment. Relapsed patients should be further stratified, such as distinguishing between early relapse (within 12 months) and late relapse groups. For early relapsed patients, clinical data strongly support CAR-T cell therapy, while late relapsed patients can prioritize glofitamab or polatuzumab-based regimens. Given the relative safety and accessibility of bispecific antibodies, despite pending long-term efficacy data, I personally prefer using bispecific antibodies before CAR-T therapy to increase the chances of a cure. At the same time, the importance of traditional immunochemotherapy and transplantation should not be overlooked, and more tailored treatment plans should be developed based on patients’ disease characteristics and financial conditions to maximize patient outcomes.

Comprehensive Management Strategies for DLBCL

Hematology Frontier: Could you share your team’s experience in managing DLBCL throughout the entire course of the disease? What innovations and developments do you foresee in the comprehensive management of DLBCL?

Dr. Zhiming Li: In China, lymphoma patients face high misdiagnosis rates and poor treatment and follow-up adherence. Studies show that only 22.1% of DLBCL patients receive standardized treatment for eight or more cycles. Lymphomas have characteristics of both chronic diseases and cancers, making comprehensive management especially important. Throughout the management of DLBCL patients, I believe in a patient-centered approach that thoroughly understands the disease characteristics and patient needs, driving treatment strategies.

At the same time, it’s crucial to keep up with international treatment trends and continuously innovate and optimize, providing safer and more effective treatments. We should tailor treatment choices and sequences based on potential changes in the disease. Additionally, it is essential to follow guideline-based practices and establish scientific and rational treatment pathways to ensure that patients receive standardized care.

Our team’s approach has transformed DLBCL treatment into a model of chronic disease health management, effectively transferring diagnostic and treatment methods to local hospitals. This way, patients receive continued standardized care even after discharge and upon returning to their local communities, ultimately guiding them toward a path to recovery.

Due to China’s vast geographical area and varying levels of medical services, comprehensive management is still in its infancy domestically and lacks systematic construction. Comprehensive management of DLBCL is a long-term endeavor. Going forward, it is necessary to promote standardized diagnosis and comprehensive management through scientific quality control standards. It is also crucial to enhance awareness among doctors and the public about the importance of standardized diagnosis and comprehensive management, especially during the rehabilitation phase. Psychological counseling and healthy lifestyle interventions should provide mental support to patients and strengthen the confidence of both patients and healthcare providers in overcoming the disease.

Dr. Zhiming Li

• Chief Physician and Doctoral Supervisor, Department of Internal Medicine, Sun Yat-sen University Cancer Center
• Chairman, Lymphoma Professional Committee, Guangdong Anti-Cancer Association
• Chairman, Comprehensive Treatment of Head and Neck Tumors Committee, Guangdong Clinical Medicine Association
• Incoming Chairman, Hematological Tumor Professional Committee, Guangdong Anti-Cancer Association
• Deputy Secretary-General and Standing Committee Member, Anti-Lymphoma Alliance, Chinese Society of Clinical Oncology (CSCO)
• Standing Committee Member, Lymphoma Professional Committee, Chinese Anti-Cancer Association
• Secretary-General and Standing Committee Member, Lymphoma Professional Committee, Chinese Association of Gerontology and Geriatrics
• Standing Committee Member, Head and Neck Tumor Expert Committee, CSCO
• Executive Member, Youth Council, Chinese Anti-Cancer Association
• Standing Committee Member, Lymphoma Sub-Committee, Chinese Medical Education Association
• Deputy Leader, Central Nervous System Lymphoma Group, Neuro-Oncology Professional Committee, Chinese Anti-Cancer Association
• Deputy Chairman, Tumor Immunotherapy Professional Committee, Guangdong Association of Integrated Traditional and Western Medicine
• Deputy Chairman, Fertility Preservation Professional Committee, Guangdong Health Management Association
• Standing Committee Member, Chemotherapy Professional Committee, Guangdong Anti-Cancer Association
• Standing Committee Member, Pharyngeal Tumor Professional Committee, Guangdong Clinical Medicine Association
• Standing Committee Member, Lymphoma Professional Committee, Guangdong Precision Medicine Application Association
• Member, Nasopharyngeal Cancer Professional Committee, Guangdong Anti-Cancer Association
• Deputy Chairman, Lymphoma Professional Committee, Guangzhou Anti-Cancer Association