From January 16 to 18, 2026, the Working Meeting of the Chinese Society of Clinical Oncology (CSCO) Leukemia, Lymphoma, and Myeloma Expert Committee and the 2026 CSCO Academic Conference on Hematologic Malignancies were held in Haikou, China. During the meeting, Professor Bing Xu of the First Affiliated Hospital of Xiamen University systematically outlined a comprehensive new framework for follicular lymphoma (FL), spanning precision risk stratification, therapeutic decision-making, and future research directions. His presentation provided valuable guidance for clinicians seeking to optimize treatment strategies and anticipate future developments in the field.Q1
Follicular lymphoma (FL) has now entered an era of precision risk stratification. Based on the latest guideline recommendations and the epidemiologic characteristics of Chinese patients, what are the key features of the current diagnostic and treatment landscape? What core logic underpins treatment selection across different disease stages and risk categories?
Professor Bing Xu:
Follicular lymphoma is a common indolent lymphoma. In China, patients tend to be diagnosed at a younger age than in Western countries, and the overall incidence is relatively lower. However, treatment outcomes are broadly comparable to those reported in Europe and the United States. At present, FL management follows a risk-adapted, stage-based strategy, with clinical staging serving as the primary basis for treatment decisions.
For patients with stage I or localized stage II disease, active treatment is generally recommended. Approximately half of these patients can achieve long-term survival—and even functional cure—through radiotherapy alone or radiotherapy combined with anti-CD20 monoclonal antibody monotherapy.
In contrast, patients with non-localized stage II, stage III, or stage IV disease are typically managed according to a “watch-and-wait” strategy, with treatment deferred until clear indications emerge.
Even among patients without immediate treatment indications, further precision risk stratification is essential. In particular, for high-risk patients, especially those with a high risk of histologic transformation, early intervention with agents such as anti-CD20 monoclonal antibody monotherapy may be considered. This approach can significantly prolong the time to next treatment and may also reduce the risk of transformation.
For patients who meet criteria for treatment initiation, current guidelines recommend either immunochemotherapy or chemotherapy-free regimens. Available evidence indicates that these two approaches yield comparable outcomes in terms of response rates, progression-free survival (PFS), and overall survival (OS). Current research efforts are therefore focused on enhancing first-line efficacy while minimizing treatment-related toxicity.
Q2
In recent years, major advances have emerged in the diagnosis and treatment of follicular lymphoma, including breakthroughs in risk assessment tools and therapeutic strategies. Which recent developments have impressed you most or are particularly impactful for the field? What overarching trends do these advances reveal?
Professor Bing Xu:
Follicular lymphoma has clearly entered the era of precision diagnosis and treatment. Traditional prognostic models—such as the Follicular Lymphoma International Prognostic Index (FLIPI), FLIPI-2, and FLIPI-PI—are no longer sufficient to fully meet contemporary clinical needs, underscoring the importance of developing more refined risk stratification systems.
For patients managed with watch-and-wait strategies, a new risk stratification framework has already been established. Based on two key factors—elevated lactate dehydrogenase (LDH) and involvement of ≥4 nodal areas—patients can be classified into low-, intermediate-, and high-risk groups. High-risk patients may benefit from early intervention with agents such as anti-CD20 monoclonal antibody monotherapy to reduce the risk of early disease progression.
For other patient populations, the recently developed FLIPI24 model represents a major advance. Published in Journal of Clinical Oncology in 2025, this model incorporates five readily available clinical variables—age, LDH/ULN, β2-microglobulin, hemoglobin (HGB), and white blood cell count (WBC)—and demonstrates superior accuracy in predicting overall survival compared with FLIPI, FLIPI-2, and FLIPI-PI. It has strong potential to become a new standard prognostic tool in follicular lymphoma.
Another critical area is the prediction of early disease progression. Progression of disease within 24 months of treatment initiation (POD24) is a well-established adverse prognostic factor, yet earlier prediction is often clinically desirable. To address this need, the Chinese Follicular Lymphoma Working Group, using Chinese patient data and machine-learning techniques, developed the FLIPI-C prognostic model, published in Biomarker Research in 2025.
This model incorporates six easily obtainable clinical parameters—LMR >10, elevated β2-microglobulin, LDH > ULN, hemoglobin <12 g/dL, involvement of >4 lymph node regions, and SUVmax >10—and demonstrates strong predictive power for POD24, outperforming FLIPI, FLIPI-2, and FLIPI-PI. Importantly, the model has also been validated in prospective Western clinical databases, where it similarly showed superior predictive performance.
Post-treatment response assessment is equally critical. In addition to achieving complete metabolic response, minimal residual disease (MRD) monitoring at the end of treatment has emerged as a key prognostic tool. When both complete metabolic response and MRD negativity are achieved, the risk of early progression is less than 7%. Conversely, when both are positive, the risk of early progression may be as high as 80%.
In summary, the diagnosis and treatment of follicular lymphoma have become fully precision-driven. Patients without immediate treatment indications can undergo refined prognostic assessment to guide surveillance strategies, while those requiring treatment can receive individualized regimens based on risk stratification. For FLIPI-C high-risk patients prone to early progression, treatment strategies can be proactively adjusted to improve outcomes. The integration of baseline risk assessment with post-treatment response evaluation forms a complete precision medicine feedback loop, ultimately enhancing therapeutic efficacy.
Q3
Looking ahead, which research directions do you believe hold the greatest promise for advancing the treatment of follicular lymphoma? Based on current clinical practice in China, how can more patients truly benefit from these cutting-edge diagnostic and therapeutic trends?
Professor Bing Xu:
Future research in follicular lymphoma is likely to focus on four key areas.
First, advancing toward more precise diagnosis and treatment. In diffuse large B-cell lymphoma, refined molecular subtyping has enabled personalized strategies such as “R-CHOP + X.” In contrast, although significant progress has been made in follicular lymphoma, the clinical translation of molecular subtyping remains incomplete. Deepening molecular understanding is a prerequisite for truly precision-guided therapy.
Second, optimizing treatment strategies for newly diagnosed patients, with the dual goals of maximizing efficacy and minimizing toxicity. At ASH 2025, the hematology team at the First Affiliated Hospital of Xiamen University reported phase II results of zanubrutinib combined with obinutuzumab (the ZO regimen) as first-line therapy for high–tumor burden follicular lymphoma. The regimen demonstrated deep and durable responses with favorable tolerability: an overall response rate of 100%, a complete response rate of 80%, and MRD negativity in 67% of patients achieving complete response. Importantly, this regimen maintained excellent efficacy while significantly reducing toxicity, making it a promising high-efficacy, low-toxicity first-line option.
Looking forward, additional first-line strategies may include earlier use of bispecific antibodies and other novel agents. Overall, chemotherapy-free regimens that deliver high efficacy, low toxicity, and improved quality of life are expected to gain increasing prominence, while the role of traditional chemotherapy in indolent diseases with long survival is likely to diminish.
Third, exploring treatment strategies for relapsed or refractory disease, particularly in patients with early progression (POD24). In these patients, conventional immunochemotherapy often yields limited benefit. Chemotherapy-free options—including EZH2 inhibitors and BTK inhibitors—have therefore become important alternatives. For patients receiving third-line therapy or beyond, or those with POD24, cellular immunotherapies such as CAR-T cell therapy and bispecific antibodies have demonstrated remarkable efficacy and are assuming an increasingly central role. The key future challenge lies in how to strategically sequence and combine therapies with different mechanisms of action, enabling patients to achieve the longest possible survival and best quality of life with the least treatment burden.
Fourth, emphasizing prospective, longitudinal disease management. As novel therapies continue to extend survival, follicular lymphoma is increasingly being managed as a chronic disease. Clinical focus must therefore extend beyond survival prolongation to encompass long-term quality of life and patient-centered comprehensive care. Only through systematic, lifelong management can survival be maximized while simultaneously preserving quality of life.
