Big coffee explores the "Australia" expert connection, talks about the new progress, new changes, and new cornerstones of inert NHL treatment

Indolent non-Hodgkin's lymphoma (NHL) is difficult to cure, and the patient will relapse repeatedly after reaching remission, and even undergo transformation
.

In 2021, the research progress in the field of indolent NHL is abundant, which provides further guidance for the treatment of indolent NHL in the future and brings new hope to more patients
.

Yimaitong invited Professor Sang Wei from the Affiliated Hospital of Xuzhou Medical University to serve as the host, and conducted in-depth discussions with Professor Huang Haiwen from the First Affiliated Hospital of Soochow University and Professor Li Ping from Shanghai Tongji Hospital on the new progress of the treatment of inert NHL in 2021
.

Professor Sangwei Indolent NHL is a more common type of chronic lymphoma.
Although indolent NHL develops slowly and the patient survives longer, it usually cannot be completely cured
.

In 2021, many international conferences (EHA/ASCO/ICML) announced a number of research progress on inert NHL, providing further guidance for the treatment of indolent NHL
.

Could you please talk about the current status of indolent NHL in my country? What is the prognosis of patients with indolent NHL? Professor Li Ping The incidence of indolent NHL in China is lower than that in European and American countries.
However, with the aging of the population, the number of confirmed cases of inert NHL has increased significantly in recent years.
Follicular lymphoma (FL) is the most common indolent NHL and has a long course of disease.
The median survival time of patients can reach 18 years, and the 10-year overall survival (OS) rate can reach 80%, but there is no complete cure
.

Most FL patients will relapse repeatedly after they reach disease remission, and with each relapse, the duration of remission (DOR) and OS will gradually shorten
.

Some patients with FL will progress early and have a poor prognosis, which is much lower than expected
.

In addition, 30%-40% of FL patients will transform into invasive diffuse large B-cell lymphoma (DLBCL).
This part of the patients has a poor prognosis, lower remission rate of salvage treatment, and significantly shortened survival time
.

In immunotherapy, Professor Sangwei should carry out detailed stratified evaluation of patients
.

At present, there is still a lack of an accurate system for the new drug era.
In the future, it is hoped that through the efforts and cooperation of major centers, an evaluation and prognosis system that is more in line with the development of the new drug era will be established
.

Would you please talk about the unmet clinical needs based on the actual situation? Professor Huang Haiwen FL's most common inert NHL, the most basic treatment plan is BR (bendamustine + rituximab), R-CHOP (rituximab + cyclophosphamide + doxorubicin) Star+vincristine+prednisone), although the overall course of the disease progresses relatively slowly, some patients will experience early progress
.

The current 10-year OS rate of FL can reach 80%, the 5-year progression-free survival (PFS) rate of patients without disease progression (POD24) within 24 months is 80.
2%, and the 5-year OS rate can reach 95%.
Once POD24 occurs, The 5-year OS rate was 63.
8%, and the 5-year PFS rate was 0.
01%
.

Rituximab is a milestone drug in the treatment of lymphoma.
After more than 20 years of development, it has been unable to break through the bottleneck of indolent non-Hodgkin's lymphoma treatment
.

The emergence of many new drugs is expected to bring new changes to the treatment of inert NHL
.

Professor Sangwei has indeed achieved milestone progress in the field of lymphoma treatment.
From early radiotherapy and chemotherapy to late rituximab, lenalidomide, otuzumab, CAR-T cell therapy products, etc.
, have been launched one after another.
May I ask about What are the current development directions for indolent NHL treatment? Professor Li Ping's anti-CD20 monoclonal antibody rituximab injection created a new era of immunotherapy for lymphoma, but there are still unmet clinical needs
.

Improving the quality of life of patients and reducing the occurrence of POD24 are problems that urgently need to be resolved in clinical practice
.

The new generation of anti-CD20 monoclonal antibody Jialuohua® (Otuzumab) has shown better clinical efficacy and safety.
It is the world's first humanized glycosylation modified type II anti-CD20 monoclonal antibody , The immunogenicity is lower, the half-life is longer and more stable, and it has stronger antibody-dependent cellular cytotoxicity (ADCC) and so on
.

At present, otuzumab is combined with a variety of drugs, including Bruton’s tyrosine kinase (BTK) inhibitors, immunomodulators (IMiD) and other related clinical studies are still underway, and otuzumab may become A new cornerstone drug in the treatment of inert NHL
.

Professor Huang Haiwen has seen an increasing incidence of indolent NHL in recent years, including FL, marginal zone lymphoma (MZL), etc.
, and even the incidence of MZL exceeds FL.
Therefore, the treatment of inert NHL needs to avoid the extremes of contempt and overtreatment
.

After the disease is relieved by first-line treatment, some indolent NHL patients still have disease recurrence
.

Therefore, exploring more effective first-line treatment options is essential to improve the long-term prognosis of patients
.

New drugs represented by the new generation of anti-CD20 monoclonal antibody otuzumab have demonstrated excellent efficacy and safety
.

The key study in which otuzumab was approved is the global phase III clinical trial GALLIUM study
.

Studies have shown that compared with the standard treatment regimen in the control group, otuzumab combined with chemotherapy can significantly reduce the risk of progression/recurrence or death by 34%, and significantly prolong PFS; the cumulative incidence of POD24 events has dropped significantly, and the risk of early progression is reduced 46 %
.

Therefore, for patients with a greater risk of early progression, it is recommended to use otuzumab combined with chemotherapy, which has sustained benefits of PFS and more obvious advantages of POD24
.

At present, the National Medical Insurance has included Otuzumab, and more and more indolent NHL patients will benefit from it
.

Professor Sangwei currently has Otuzumab available in China.
Please combine the recent research progress to share the application prospects of Otuzumab and talk about your views
.

In addition to the initial treatment of FL approved by Professor Li Ping in China, otuzumab also showed good efficacy and safety in relapsed and refractory FL
.

The GADOLIN study showed that compared with bendamustine single-drug regimen, otuzumab combined with bendamustine regimen can significantly improve PFS and OS in patients with relapsed and refractory FL, and can reduce disease progression, recurrence, and recurrence by 43%.
Risk of death, and no unexpected safety incidents occurred
.

The results of the Phase II study of otuzumab combined with lenalidomide regimen in the treatment of newly-treated FL patients are also surprising.
The two-year PFS rate is as high as 96%, with a median follow-up of 25 months, and the complete remission (CR) rate 94%, and the entire program is free of chemotherapy, and its safety is more advantageous than traditional chemotherapy programs
.
Long-term follow-up data are expected .

According to Professor Huang Haiwen, in almost all clinical trials of indolent NHL, a combined treatment plan of Otuzumab and related therapeutic drugs will be used, and major domestic and foreign guidelines have gradually included Otuzumab as the treatment recommendation for FL With the advancement of medical insurance policies, more and more patients benefit from otuzumab
.

With the widespread application of more and more immunological drugs, Professor Sangwei, inert NHL can basically achieve chemotherapy-free (chemo-free) treatment
.

May I ask, what are your prospects for the treatment of indolent NHL in the future, and what are your expectations for chemo-free? Professor Huang Haiwen has a higher cure rate for indolent NHL such as FL, and patients can survive for a long time
.

However, if cytotoxic drugs are selected in treatment, the incidence of second tumors will increase as the patient's treatment cycle extends
.

At present, there are more and more cases of myeloid tumors caused by the treatment of other tumors in clinical treatment.
Choosing a chemo-free treatment plan can reduce the incidence of secondary tumors and adverse events, so that patients have a better quality of life.

.

The exploration of chemo-free has been at the forefront and is a major trend in the future.
Although chemotherapy is still in an important position at this stage, the future direction of treatment must be chemo-free, and the drug should be stopped after cure to improve the quality of life of patients
.

Although Professor Li Ping’s chemotherapy is still the cornerstone therapy at present, the exploration of chemo-free must be the general trend in the future, especially for inert NHL such as FL and MZL.
The cure rate itself is very high and patients can survive long-term, so the curative effect is the same.
Under the circumstances, more inclined to choose a more secure solution
.

In addition, cellular immunotherapy represented by CAR-T is also a very hot topic now.
Related domestic and foreign studies have shown that CAR-T therapy has shown very good efficacy in inert NHL
.

Professor Sangwei looks forward to the establishment of a more accurate hierarchical diagnosis system in the future, and an evaluation and prognosis system that is more in line with the development of the new drug era
.

Chemo-free is an eternal pursuit.
It is expected that more and more lymphoma subtypes will be treated to make progress, and the quality of life of patients will be improved through multi-center cooperation
.

Expert profile Professor Sang Wei, MD, associate professor, deputy chief physician, master supervisor, deputy director of the Cell Research and Translational Medicine Center of Xu Medical Affiliated Hospital, deputy director of the Department of Hematology, Xu Medical Affiliated Hospital, director of the Hematology Branch of the Chinese Medical Association, Lymphoma Ward Member of the Lymphocytic Disease Group Member of the Lymphoma Special Committee of the Chinese Anti-Cancer Association Secretary-General of the Chinese EBV-related Disease Working Group Member of the 1st T-cell Lymphoma Working Group Member of the Lymphoma Group of the Hematology Branch of the Chinese Geriatrics Association Vice Chairman of the Jiangsu Lymphoma Alliance Member of the Lymphoma/Myeloma Group of the Hematology Branch of the Jiangsu Medical Association Member of the “Six Talents of Jiangsu Province” "Gaofeng" training target: Professor Huang Haiwen, a young medical talent in the "Science and Education Strengthening Health Project" in Jiangsu Province, and a master's supervisor, Chief Physician of the Department of Hematology, The First Affiliated Hospital of Soochow University, member of the Lymphocytic Disease Group, Chinese Medical Association, Chinese Medical Association Member of the Lymphatic Hematology Group, China Medical Education Association, Deputy Chairman, Lymphoma Professional Committee, China Anti-Cancer Association, Hematological Oncology Committee, Lymphoma Group Member, Chinese Anti-Cancer Association, Chronic Lymphocytic Leukemia Working Group, Deputy Director, Jiangsu Lymphoma Professional Committee Committee Member, Vice Chairman of Jiangsu Lymphoma Alliance, Member of Lymphoma Myeloma Group, Hematology Branch of Jiangsu Medical Association Professor Li Ping, Chief Physician of Department of Hematology, Tongji Hospital, Shanghai, Doctor of Medicine, Nagoya University, Master Supervisor, Postdoctoral Doctor of Chinese Medicine, Aichi Cancer Hospital, Japan Hematology Branch Youth Committee Member of China Anti-Cancer Association Council Youth Committee Member of Lymphoma Professional Committee of Chinese Association of Anti-Cancer Association Committee Youth Committee Member of the Lymphoma Professional Youth Committee of Shanghai Anti-Cancer Association Member of the Laboratory Diagnostics Group of the Shanghai Society of Hematology Member of the Hematology Committee of the Shanghai Society of Immunology For the past 5 years, he has been mainly engaged in the diagnosis and treatment of lymphatic tumors and CAR-T immunization Treatment
.

Currently presides over 2 National Natural Science Foundation of China, participated in a number of national projects and Shanghai Science and Technology Commission projects, published more than 30 papers ★ Scan the QR code below to enter the "Mystery Exploration" channel ★Pick "Read the original text" and enter the "Mystery" Discovery Channel!