Big coffee explores "Australia" experts talk about the frontier of EHA: FL challenges, changes and opportunities

The epidemic has not stopped, but academics are supreme
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Recently, the 26th European Annual Meeting of Hematology (EHA) online conference was successfully held from June 9th to June 17th
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The EHA annual meeting announced a number of research progresses related to follicular lymphoma (FL), which provided further guidance for treatment
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This time Yimaitong invited Professor Qu Changju from the First Affiliated Hospital of Soochow University as the host.
Together with Professor Liu Ligen from Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Professor Yu Wenjuan from the First Affiliated Hospital of Zhejiang University School of Medicine discussed the FL’s meeting at this year’s EHA meeting.
Hot topics and new developments were discussed in depth
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Professor Qu Changju Q1: Professor Liu Ligen, first of all, would you please talk about the current status of FL in my country and what is the prognosis of FL patients? Professor Liu Ligen FL is the second most common lymphoma subtype
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In recent years, the incidence of FL in China has been increasing year by year, and it has begun to show a trend of younger age.
Although the median age of FL patients is 65 years old, today, clinical FL cases in their 40s and 50s are gradually normalizing
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Clinicians are not paying enough attention to FL.
In their inherent impression, FL has a longer course of disease and a better prognosis.
It is more for FL patients to wait for observation and wait for treatment indications before intervention
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For FL patients with indications for treatment, the overall curative effect is good, but patients with high tumor burden or young onset are relatively easy to progress and have a poor prognosis.
This is also a problem for hematologists to solve
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Professor Yu Wenjuan currently has some unsatisfied treatment needs for FL in China: When POD24 occurs, patients are prone to disease progression, and survival rate and overall survival (OS) are significantly reduced; second, high-risk FL patients often have a poor prognosis, but At present, there is no effective treatment method.
The treatment strategy and the timing of intervention for high-risk patients are one of the problems that need to be solved urgently.
Once the condition of the patients waiting to be observed increases rapidly, the choice of treatment options is also worthy of further exploration; Ⅰ/Ⅱ After FL patients receive local radiotherapy or surgical resection, whether they need immunotherapy or immunotherapy combined with chemotherapy, these questions will need to be answered by clinicians in the future
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Professor Qu Changju Q2: At present, most FL patients are incurable.
Although FL has a good prognosis and slower clinical progress, it is also easy to relapse repeatedly
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Clinically, about 20% of patients will have early recurrence (POD24), and the prognosis of this part of patients is very poor
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How to identify POD24 early is also the primary problem that needs to be solved urgently at present for follicular lymphoma
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Based on your years of clinical experience, what methods can be used to identify patients who may have POD24 at an early stage? Professor Liu Ligen indeed, POD24 is an issue of great concern in recent years
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The prognosis of FL patients is good.
Once POD24 occurs, the prognosis of patients will be greatly reduced
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FL and other hematological tumors have similarities, that is, a high degree of heterogeneity
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Nowadays, the classification of tumors is usually based on the location of the disease.
In the future, it may be classified entirely by molecular characteristics.
This will be a revolutionary change.
For example, the molecular characteristics of lung cancer patients are exactly the same as those of FL patients.
The two patients may use the same Kinds of programs to treat
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POD24 should do more in-depth exploration of the molecular characteristics of cells at the genetic level.
Hospitals with conditions can use cryodissection, genetic identification, and comparison of FL tumor cells with cases of different tumor types.
Work in this area is still There is not much information
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At this year's EHA conference, the EP802 study analyzed the heterogeneity of high tumor burden follicular lymphoma (HTB-FL).
The researchers used PET-CT commonly used in clinical practice to conduct in-depth exploration of POD24
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Studies have shown that early PET-CT assessment can identify patients who may have POD24.
Early PET-CT negative patients are associated with a good prognosis.
Early PET-CT positive patients may be the potential population of POD24
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Due to the high popularity of PET-CT in clinical practice, this research has important guiding significance for clinical application
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Professor Qu Changju I found out that local clinicians attach great importance to PET-CT testing at MD Anderson Cancer Center in the United States
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Domestic clinicians pay relatively little attention to PET-CT detection due to their heavy workload
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The results of previous studies have shown that FL patients with an SUV value> 13 under the PET-CT test have a higher probability of disease conversion, and this part of FL patients has a poor prognosis
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It is not clear that the relationship between FL patients and POD24 patients who are prone to disease transformation, but the relationship between the two deserves further research and exploration
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All in all, PET-CT detection has a high value for the treatment of FL, and it is a treatment tool that should be paid attention to in the clinical treatment of FL
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Professor Qu Changju Q3: Is there any research progress on the risk prediction of POD24 in FL patients at the recently concluded EHA conference? In terms of your clinical experience, what is the significance of this progress? At this EHA meeting, Professor Yu Wenjuan published a systematic review and meta-analysis by Professor Zhang Huilai’s team from Tianjin Medical University Cancer Hospital to analyze the risk factors of POD24 in previously untreated FL patients to determine the potential of POD24 in newly-treated FL patients Risk factors
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A comprehensive literature search was conducted in Embase, Medline, and Cochrane Library databases, to screen the prognostic studies of newly diagnosed FL patients with 1-3A grades, and analyze the high-risk risk factors related to POD24
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A total of 96 studies were included in the study, and 11 factors were meta-analyzed
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Meta analysis results showed: sIL-2R increased (HR 2.
48; 95% CI, 1.
74-3.
54; p<0.
0001), TMTV> 510mL (HR 2.
17; 95% CI, 1.
60-2.
95; p <0.
0001), β2m increased (HR 4.
14; 95% CI, 2.
07-8.
28; p<0.
0001), increased LDH (HR 3.
05; 95% CI, 1.
63-5.
71; p=0.
0005,), pathology grade 3a (HR 2.
22; 95% CI, 1.
31 -3.
74; p=0.
0030), lymphoma-related macrophages/high power field (LAM/HPF) ≥15 (HR 4.
13; 95% CI, 1.
92-8.
88; p=0.
0003), vitamin D deficiency (<20ng/ml) (HR 2.
66; 95% CI, 1.
44-4.
92; p=0.
0020) was significantly associated with an increased risk of POD24
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Absolute lymphocyte count/absolute mononuclear cell count (ALC/AMC) (cutoff: 4.
7), gender, EZH2 mutation status, and effector T cell gene expression characteristics (Teff signature) were not significantly correlated with POD24
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This study is the first meta-analysis to comprehensively analyze the risk factors related to FL patients and POD24, which is of clinical significance
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Professor Qu Changju Q4: In addition to clarifying the risk factors for progression and detecting early progression in time, new drugs and new usage also play an important role in improving the prognosis of FL patients
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Not long ago, otuzumab was approved in China for the treatment of FL, bringing new hope to many FL patients in China
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Could you please introduce the new research progress of Otuzumab (GA101) in follicular lymphoma at this year's EHA conference? Professor Liu Ligen's treatment of hematological tumors has benefited from the development of the industry, and the pharmaceutical field provides effective weapons for clinical use
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The GAZELLE study is a prospective, open-label, multi-center, single-group, phase IV clinical study, which included 113 newly-treated FL patients, and no grade ≥3 occurred after the first cycle (C1, standard infusion rate) treatment Patients with infusion-related reactions (IRR) receive a 90-minute rapid infusion of Otuzumab (SDI) starting from C2
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The safety of patients with FL who received Obi 90-minute SDI from C2 was evaluated
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The primary endpoint is the incidence of IRR ≥ grade 3 during C2
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Secondary endpoints include adverse events (AE) and the overall response rate (ORR) at the end of induction as assessed by the researchers at the end of induction (EOT)
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The results of the study showed that among the 110 patients who received Otuzumab SDI after the onset of C2, none of the patients had an IRR level ≥3 caused by SDI in C2
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Only one patient had SDI-related grade 3 IRR in C5, which was manifested by hypertension
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Other IRR using SDI was 1/2 grade, and no 4/5 grade IRR occurred
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Other AEs are similar to those previously reported
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In terms of efficacy, at the clinical deadline, 104 patients were evaluated for effectiveness at EOI, 67.
3% of patients achieved complete remission (CR), and 19.
5% achieved partial remission (PR)
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Based on the current research progress, otuzumab is expected to have a place in indolent lymphomas including FL, bringing patients safer treatment and longer survival
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Professor Yu Wenjuan's current FL treatment drugs, such as BTK inhibitors and BCL-2 inhibitors, have not shown their efficacy in the treatment of mantle lymphoma, chronic lymphoma, and even some diffuse large B-cell lymphomas
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While the GAZELLE study guarantees safety, the efficacy data is accurate, which greatly increases the confidence of doctors and patients in treatment
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The research progress is not only the update of numbers, for patients, otuzumab is a completely innovative drug
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Professor Qu Changju Q5: In view of the excellent efficacy and safety of Otuzumab in related studies, what are your prospects for the application of Otuzumab in follicular lymphoma? Professor Liu Ligen’s overall development direction for FL treatment is a chemo-free regimen.
Otuzumab is a promising new drug in the future “territory” of FL treatment in China, and its application prospects are very worth looking forward to
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Combination therapy with otuzumab for high-risk/poor prognosis patients may improve the long-term survival and depth of remission of these patients
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Professor Qu Changju's chemotherapy-free regimen has shown good results in many diseases such as diffuse large B-cell lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia
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The approval of otuzumab undoubtedly provides more treatment options for the exploration of FL non-chemotherapeutic regimens, enabling more FL patients to benefit from it
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Expert Profile: Professor Liu Ligen, Chief Physician, Director, and Master's Tutor of the Department of Hematology, Shanghai Jiao Tong University Tongren Hospital, Director of the Intern Diagnosis Teaching and Research Office, Department of Laboratory Medicine, School of Medicine, Shanghai Jiao Tong University, Member and Secretary of the Hematology Branch of the Shanghai Medical Association Deputy Committee of Hematology and Immunology, Shanghai Society of Immunology Chairman, Shanghai Anti-Cancer Association, Vice Chairman, Infection and Chemotherapy Branch, Shanghai Medical Association, Standing Committee, Academic Branch, Shanghai Association of Integrative Medicine, Member of Blood Branch, Shanghai Association of Chinese Medicine, Chinese Medical Doctors Association, Branch of Integrative Medicine Physicians, Oncology Member of the Hematology Committee of the Chinese Society of Chinese Medicine Standing Committee Member of the Hematology Branch of the Chinese Medical Doctor Association Member of the Tissue Cell Disease Committee Member of the Hematology Committee of the Chinese Anti-Cancer Association Member of the Myeloid Group Member of the Hematology Branch of the Chinese Society of Geriatrics Member of the Chinese Rehabilitation Medicine Member of the Society of Hematology, National Natural Science Foundation of China, Reviewer of National and Shanghai Science and Technology Awards, Reviewer of "Thrombosis and Hemostasis", Reviewer of International Journals such as Apoptosis, 34 years of clinical experience in hematology, good at myeloid tumors, lymphatic system Diagnosis and treatment of tumors, myeloma, thrombosis and hemostatic diseases
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He has presided over the National Natural Science Foundation of China's general projects, the Shanghai Municipal Commission of Science and Technology and 10 district bureau-level projects, published 66 papers, including 11 SCI papers, participated in the editing of 8 monographs, including 3 associate editors
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Professor Yu Wenjuan, Clinical Doctor, Deputy Director of Department Administration, Chief Physician, Master's Supervisor, Deputy Director, Hematology and Tumor Committee of China Anti-Cancer Association, Member of CSCO Anti-leukemia Alliance & Anti-Lymphoma Alliance Youth Committee, Member of Hematology and Lymphology Committee of Chinese Association of Women Physicians Member of the Expert Committee of the Bethune Foundation Academy Member of the Chinese Geriatric Hematological Lymphoma Group Member and Secretary of the Hematology Branch of Zhejiang Medical Association Member and Secretary of the 10th Committee of the Hematology Branch of Zhejiang Medical Association Youth Member of the Editorial Board of the Chinese Journal of Hematology In 2016, he won the first prize of Zhejiang Science and Technology Progress Award.
Professor Qu Changju, Associate Chief Physician, First Affiliated Hospital of Soochow University, Doctor of Medicine, MD Anderson Cancer Center, USA Postdoctoral Fellow, Sylvester Comprehensive Cancer Center, Miami University, USA Member of the Standing Committee of the Hematopoietic Stem Cell Transplantation and Immunotherapy Professional Committee of Jiangsu Research Hospital Member of the Jiangsu Anti-Lymphoma Alliance Member of the Jiangsu Shen Research Hospital Association Cell Therapy (CAR-T) Professional Committee Member of the Fifth Batch of Gusu Health Young Top Talents 2011 and 2012 He was awarded the "Achievement Award" twice a year by the American Hematology Annual Meeting.
In 2013, he was awarded the "Performance Reward" by the MD Anderson Cancer Center of the United States.
He presided over 3 projects from the National and Jiangsu Natural Science Foundation and Suzhou City, and participated in more than 10 domestic and foreign projects.
JCI, Blood and other journals have published more than 20 SCI papers, and the first author or corresponding author has more than 10 references: 1.
2021 EHA conference abstract number: EP802.
2.
2021 EHA conference abstract number: EP794.
3.
2021 EHA conference abstract number: EP807 .
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