Professor Xu Bing: The treatment of FL should have a "strategic vision", and comprehensive consideration of treatment options is the key| the 7th International Summit Forum on Anti-leukemia and Lymphoma

Medical Pulse: FL is an indolent lymphoma that cannot be "cured" at present and is prone to recurrence
.
Accurate identification of high-risk patients is essential
to improve the efficacy of FL.
Could you briefly talk about the commonly used prognostic stratification systems for FL, and what are the risk factors for FL prognosis that are worth paying attention to?

FL is a common indolent lymphoma, the second most common subtype of lymphoma, after diffuse large B-cell lymphoma
.
The overall survival of FL is good, the 5-year overall survival (OS) rate can reach about 90%, and most patients can survive for more than
10 years.
However, 5% of patients have a refractory primary disease, and another 20% have disease progression (POD24) within 24 months of initial treatment, which has a poor prognosis, so it is important to accurately identify high-risk patients
.

At present, the clinical prognostic models of FL include FLIPI-1, FLIPI-2, PRIMA-PI and FLEX, among which the FLEX model is relatively good in sensitivity and specificity, but because it contains nine indicators, the tumor diameter product (SPD) and the number of NK cells are difficult to measure, so the operability is poor; The FLIPI-1 model is better suited for predicting OS; The FLIPI-2 model is better suited for predicting progression-free survival (PFS).

In addition, FL clinical prognostic models also include m7-FLIPI and 23 gene prognostic models, but these scoring systems are not very operable at this stage and cannot be routinely applied to clinical practice
.

At present, the relationship between tumor immune microenvironment and POD24 is still worth exploring
.
Our team recently published a study in top international journals to explore the evolution of the tumor immune microenvironment in patients with early FL progression, which may be closely related
to the occurrence of POD24.

In general, there is currently no particularly good prognostic model that can accurately predict POD24, and the general clinical will predict all the models that can be applied, if they are all high-risk, combined with whether it is a large mass, the number of lymph node affected sites, the medium-term efficacy and the efficacy evaluation after treatment, so as to predict POD24
more accurately.

In addition to accurately identifying high-risk patients, appropriate treatment strategies are also very important
to improve the efficacy of FL.
High-risk treatment-naïve patients are usually at higher risk of early disease progression and have a poor
prognosis.
Could you please briefly talk about the treatment options for high-risk treatment-naïve FL patients? And what are the new drug developments worth paying attention to?

Since about 20% of FL patients have a poor prognosis and are difficult to identify, treatment strategies should be changed for high-risk treatment-naïve FL patients to reduce the occurrence of POD24 as much as possible and improve the prognosis
of overall FL patients.
In the choice of CD20 monoclonal maber: obinutuzumab is recommended as an alternative to rituximab
in intermediate- and high-risk patients.
The GALLIUM study confirmed that for patients with intermediate- and high-risk FL, obinutuzumab combined with chemotherapy can reduce the incidence of POD24 by about
50% compared with rituximab combined with chemotherapy 。 In the choice of chemotherapy regimen: the patient should be analyzed on a case-by-case basis, and when the patient is a large mass or has a high baseline SUV value of grade 3A FL or PET-CT, the obinutuzumab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP) regimen can be selected; In other cases, bendamustine is also a good choice because of its relatively small side effects and good efficacy; For FL patients with EZH2 mutations, the current study confirms that the CHOP regimen is more effective than bendamustine
.

In terms of new drug progress, the efficacy of the first-line treatment of obinutuzumab combined with lenalidomide has been confirmed, with an effective rate of about 90% and a complete response (CR) rate of about 70%, and this program is also worth trying
.

Yimaitong: For patients with relapsed/refractory FL after treatment, how should the treatment plan be chosen? And what are the new drug developments worth paying attention to?

Since the vast majority of FL patients cannot be cured, and 80% of patients will have recurrence, the choice of treatment plan at the time of recurrence is particularly important, and "strategic vision" should be obtained: for patients with low tumor burden, small mass, and no high-risk factors at recurrence, the strategy of observation and waiting can be used; For patients who are indolent, have been in remission for a long time, and relapse, the original regimen can be continued, but if bendamustine has been used in the past, it is not recommended to use it again, and generally the second use of bendamustine is not effective, so it can be substituted between bendamustine, CHOP regimen, and lenalidomide-containing regimen; For patients with early progression or high refractory treatment, the traditional regimen may not be effective, at this time, the choice of regimen can be carried out according to the age of the patient, if it is a young patient, autologous hematopoietic stem cell transplantation can be used, if it is an elderly patient, the regimen containing lenalidomide can be used or some new targeted drugs (PI3K inhibitors, EZH2 inhibitors, etc.
) can be selected; In addition, CAR-T therapy and bispecific antibodies are also very good choices
for patients with relapsed/refractory FL.

In summary, clinicians should consider holistics in the choice of treatment for patients, taking into account the overall treatment strategy
of the second, third, and even later line.
Although there are many new drugs for the treatment of FL, it is recommended that non-high-risk patients do not choose too many new drugs, and the replacement application of traditional drugs can be sufficient; For high-risk patients, some new drugs can be selected to improve prognosis
.

Professor Xu Bing

• Second-level chief physician, professor, doctoral supervisor

• Expert of special allowance of the State Council

• Young and middle-aged experts with outstanding contributions from Fujian Province

• Director of the Department of Hematology, Xiamen University, Director of the Institute of Hematology, Xiamen University

• Member of the First Affiliated Hospital of Xiamen University, Director of the Department of Hematology, Director of the Internal Medicine Teaching and Research Office, and Director of the Internal Medicine Training Base

• Member of the Standing Committee of the Hematologist Branch of the Chinese Medical Doctor Association

• Leader of the Chinese Working Group on Follicular Lymphoma

• Member of the Standing Committee of the Hematological Oncology and Lymphoma Professional Committee of the Chinese Anti-Cancer Association

• Chairman of the Leukemia Academic Working Committee of the Chinese Geriatrics Society

• He has won 1 first prize and 3 second prizes of provincial and ministerial science and technology progress awards, presided over 5 projects of the National Natural Science Foundation of China, and published more than 200 papers in BLOOD, JHO and other journals as the first or corresponding author, including more than 70 SCI papers, 27 papers with more than 5 points, 6 papers with more than 10 points, and the total impact factor reached 369 points