2022CSH Professor Qiu Lugui: Grasp the basics, pay attention to the progress, China's lymphoma treatment prospects are broad

Listening to the sound of blood and perceiving the rhythm of life, the much-anticipated "17th National Hematology Academic Conference of the Chinese Medical Association" will be grandly opened
on September 23-25, 2022 at the National Convention and Exhibition Center in Shanghai.
The conference was hosted by the Chinese Medical Association and the Hematology Branch of the Chinese Medical Association, hosted by the Shanghai Medical Association, co-organized by Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, the First Affiliated Hospital of Soochow University, and the Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, with the theme of "respect, inheritance, collaboration and innovation", specially invited famous experts at home and abroad to talk about the latest progress
in the field of blood diseases.
On this occasion, Professor Qiu Lugui of the Blood Disease Hospital of the Chinese Academy of Medical Sciences is invited to share his insights on
the current situation, the latest treatment progress and future development prospects of the field of lymphoma.

Medical Pulse Tong: As a clinical expert who has been working in the field of lymphoma for many years, you have brought many contributions to this field, can you please combine your clinical experience to briefly introduce the current situation of lymphoma treatment in China, and what clinical needs are still unmet?

With the aging of the population and the change of disease spectrum, the incidence of lymphoma in China has continued to rise, which has exceeded 8/100,000, and there are about 100,000 new cases of lymphoma patients every year, and lymphoma has become the most common malignant tumor in the
blood system.
With the economic and social development in recent years, the accessibility of new drugs has improved, and the level of lymphoma diagnosis and treatment in China has gradually improved, and the survival of patients has been prolonged
.
However, due to the imbalance of economic and social development and other issues, there are still large differences between the level of diagnosis and treatment and the survival of patients in China compared with the international advanced level, and the 5-year total survival (OS) rate of lymphoma patients in the United States and Japan is 68.
1% and 57.
3% respectively, while the 5-year OS rate of lymphoma patients in China is only 38.
4%¹
.
The level of accurate diagnosis and standardized diagnosis and treatment in China still needs to be improved
.

Lymphoma is the most common malignant tumor of the blood system, the continuous emergence of new drugs has brought new hope to lymphoma patients, can you please share the new progress of lymphoma treatment with us?

As a hematologic disease, the incidence of lymphoma is not equal to that of all types of lymphoma, and the prognosis of patients varies greatly
.
Some indolent lymphomas have a better prognosis, and a few patients may even go without treatment
for life.
However, aggressive lymphoma requires aggressive treatment, and some lymphoma patients with very poor prognosis still fail to improve
prognosis under existing treatments.

For the treatment of lymphoma, accurate diagnosis is crucial, and only accurate diagnosis can lead to the correct treatment
.
More and more patients with indolent lymphoma such as chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL) are diagnosed by physical examination route, and the treatment indications of different diseases are different, and in the absence of treatment indications, premature intervention and treatment until there are treatment indications, and the survival outcomes are similar, therefore, the treatment of lymphoma first needs to be carried out under the premise of accurate diagnosis and mastery of treatment indications
.
The choice of molecularly targeted drugs and therapies in lymphoma patients also requires pathological diagnosis guidance, and the improvement of drug selection accuracy depends on the improvement
of pathological diagnosis.
Nowadays, pathological diagnosis is no longer limited to morphological diagnosis, but also closely integrated
with flow cytometry, immunohistochemistry, cytogenetics, genomics and so on.
Accurate diagnosis also requires the combination of imaging analysis, and after diagnosis, comprehensive analysis is carried out with the patient's clinical features, age, physical status and socio-economic situation, etc.
, to select the appropriate diagnosis and treatment plan
for the patient.

The standardized treatment of lymphoma has a lot of room
for improvement and development.
The treatment of indolent lymphoma requires mastery of treatment indications, and patients without treatment indications should undergo regular follow-up and observation to ensure the quality of life of patients and save medical resources
.
DLBCL is the most common invasive lymphoma, in general, the treatment of DLBCL patients in China is not standardized, but based on the standard treatment regimen of R-CHOP, combined with the patient's prognostic stratification, biological characteristics, etc.
, increase or decrease the corresponding drugs or doses for treatment, and the cure rate of patients can reach more than
50%.
The results of a recent large cohort study of more than 500 patients with DLBCL in our center showed that the 5-year OS rate > 70%, of which the 5-year OS rate of patients without adverse prognostic factors reached 90%; The 5-year OS rate in young, high-risk patients can also reach 70%.

Therefore, prognostic stratification and standardized treatment based on accurate diagnosis can significantly improve the cure rate or long-term survival rate of
lymphoma patients.

In recent years, the progress of lymphoma treatment has been mainly divided into two categories, the first is the progress
of small molecule targeted drugs.
Through the in-depth study of tumor pathogenesis, it is found that the continuous activation of a series of kinases in B cell receptors and their downstream channels makes tumor cells continue to proliferate and anti-apoptosis, and a variety of small molecule targeted drugs developed for this series of key kinases have changed the overall treatment strategy
of indolent B cell lymphoma to some extent.
BTK inhibitors have achieved good efficacy
in CLL, Fahrenheit macroglobulinemia (WM), mantle cell lymphoma (MCL), and MZL.
PI3Kδ inhibitors have achieved remarkable efficacy in FL for the treatment of relapsed refractory (R/R)FL, with an objective response rate (ORR) of more than 80%, and in the future, it can continue to be explored
in CLL, MCL, WM, peripheral T-cell lymphoma, GCB DLBL and other diseases.
BCL-2 is a key molecule in the apoptotic signaling pathway, and due to its high activation, tumor cells cannot be apoptotic, resulting in continuous accumulation of
tumor cells.
BCL2 inhibitors, as a broad-spectrum antitumor agent, have demonstrated good efficacy
in CLL, WM, high-risk MCL, DLBCL, and elderly acute myeloid leukemia.
The emergence of drugs targeting the NFκB signaling pathway, including proteasome inhibitors such as bortezomib, immunomodulators such as lenalidomide, AKT inhibitors, etc.
, has gradually changed the lymphoma treatment model
.

The second category is the progression
of immunotherapy against tumor cell antigens.
The development of immunotherapy has gone through a long time, and the anti-CD20 monoclonal antibody rituximab that has been on the market for more than 20 years is one of the successful models of immunotherapy, which significantly improves the prognosis and survival of B-cell lymphoma and has become the cornerstone drug
of B-cell lymphoma treatment.
In recent years, the development of immunotherapy has focused on antibody drug conjugates (ADCs), bispecific antibodies, and CAR-T cell therapy
.
At present, targets for B cells include CD19, CD20, CD22, CD79α, etc.
, which can play a role through naked antibody, and when the naked antibody therapy effect is not good, it can exert antitumor effect
by combining with cytotoxic drugs.
Bispecific antibodies, such as tumor antigens (such as CD19) & CD3 bi-target antibodies, enter the body and activate endogenous T cells to exert anti-tumor immunotherapy effects
.
CAR-T cell therapy is a new type of immunotherapy with high attention and rapid progress, CD19 CAR-T has been successfully marketed, and CD20 CAR-T and CD22 CAR-T are also under development
.
In addition to the single-target CAR-T, researchers are also exploring the existence of a more effective dual-target CAR-T through technological transformation, such as combined with PD-1 to enhance T cell activity and duration
.
Not only the treatment of B-cell lymphoma is constantly improving, but also the treatment of T-cell lymphoma is developing, although the progress is relatively slow, but the targeted CD5, CD7, CD30 and other immunotherapies are gradually developing
.
The exploration of immunotherapy is in the ascendant, constantly bringing new hope
to lymphoma patients.

As a doctor who has been engaged in the field of hematology and oncology for a long time, it is particularly important
not only to pay attention to the progress of new drugs, but also to do a good job in the basic work, that is, accurate diagnosis and standardized treatment.
Doing a good job of basic work can enable most patients to obtain longer survival, and even cure, based on this, the new drug will first be applied in patients with relapsed refractory lymphoma, and then gradually explore the front line, and finally achieve the goal
of improving the cure rate and long-term survival rate of front-line high-risk patients.
In summary, grasp the foundation, pay attention to progress, comprehensively, scientifically and rationally apply various treatment methods, and strive
to obtain the best curative effect, the longest survival and maximize the health economics for patients.

Medical Pulse Pass: Based on the current status quo and treatment progress in the field of lymphoma, what are your expectations or prospects for the treatment prospects of lymphoma patients in China?

It is hoped that with the country's economic and social development and the improvement of medical conditions, more and more patients will be able to obtain early diagnosis, and it is a precise diagnosis
.
The doctor's concept is further improved, and various types of new drugs are reasonably applied on the basis of accurate diagnosis, prognostic stratification, and standardized treatment, so that patients can obtain longer progression-free survival from first-line treatment, and can also obtain remission after disease progression, and once again obtain longer survival, and even cure
.
Improve the overall level of lymphoma diagnosis and treatment in China, bring cure to more patients, and provide high-quality long-term survival
for patients who cannot be cured.

Professor Qiu Lugui

• Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences)

• Director of Lymphoma Diagnosis and Treatment Center, Chief Physician, Doctoral Supervisor

• Director of Tianjin Cord Blood Hematopoietic Stem Cell Bank

• Experts who enjoy special government allowances from the State Council

• Member of the International Myeloma Society Membership Committee

• Member of the International Myeloma Working Group Expert Committee

• Member of the Editorial Board of Blood Advances Magazine

• Chairman of the Hematology and Oncology Professional Committee of the Chinese Anti-Cancer Association

• Vice President of Lymphoma Research Alliance of Chinese Society of Clinical Oncology

• Vice Chairman of the Hematology Committee of the Association of Integrative Physicians

• Vice Chairman of the Hematology Professional Committee of the Chinese Medical Education Association

• Chairman of the Hematology and Tumor Professional Committee of Tianjin Anti-Cancer Association

• He is a member of the editorial board of 6 core journals including the Chinese Journal of Hematology

• He has completed more than 20 fund projects such as key projects of the National Science and Technology Support Program and the National Natural Science and Technology Key Project

• He has published nearly 500 papers, including more than 140 SCI papers

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