2022 CSH Professor Yi Shuhua: Cracking the treatment dilemma of mantle cell lymphoma, we are on the way

Listening to the sound of blood and perceiving the rhythm of life, on September 23-25, 2022, the "17th National Hematology Academic Conference of the Chinese Medical Association" was grandly opened
at the National Exhibition and Convention 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 Yi Shuhua of the Blood Disease Hospital (Institute of Hematology) of the Chinese Academy of Medical Sciences was invited to explain the current situation
of diagnosis and treatment and development of mantle cell lymphoma (MCL) for us.

Yimaitong: Can you please introduce the current diagnosis and treatment status of MCL? And what challenges remain?

MCL is a relatively rare non-Hodgkin lymphoma (NHL) subtype, accounting for only 6% to 8% of NHL, so missed diagnosis is a relatively common problem in the diagnosis of MCL
.
In 2022, the WHO will mainly divide MCL into classic MCL, leukemia-like non-lymphadenoid MCL and in situ MCL
.
Pathology is the gold standard for MCL diagnosis, mainly based on the typical histomorphological characteristics of MCL combined with mature B cell immune characteristics, plus immunohistochemical CD5 and Cyclin D1 intranuclear positive
.
Patients with MCL usually present with extensive lymphadenopathy, lymph node biopsy is more beneficial for diagnosis, and Cyclin D1 immunohistochemistry is usually positive
.
For leukemia-type non-lymph node MCL, such as tumor cell immunophenotype conforming to typical MCL, routine chromosomal karyotyping analysis, or fluorescence in situ hybridization (FISH) detection of t(11; 14) MCL
can also be diagnosed.
MCL extranodal organ involvement is common, such as gastrointestinal tract, bone marrow and peripheral blood infiltration, which requires the attention
of clinicians and pathologists.

In recent years, with the deepening of the understanding of MCL, the treatment of MCL has made important progress
.
The release of the consensus of the relevant guidelines of the MCL has greatly promoted the clinician's understanding of the disease and provided a basis for the standardized diagnosis and treatment of MCL
.
However, in actual clinical work, the standardized diagnosis and treatment of MCL still faces certain challenges
.
For example, the proportion of domestic MCL first-line autologous hematopoietic stem cell transplantation treatment is only about 20%, while the proportion in Europe and the United States is 30%-40%.

In recent years, with the development of new drugs, targeted drugs represented by BTK inhibitors have opened up a new situation in the treatment of MCL
.
At present, many approved BTK inhibitors have shown good remission rates and survival periods
.
The application of BTK inhibitors in the first-line treatment of MCL is being explored, and it is expected to enter the first-line treatment from the second line in the
future.
In addition, for high-risk MCL patients, the existing treatment options have limited efficacy, and the survival period of patients is only 2-3 years, and it is urgent to explore new treatment strategies to break through the dilemma
.

Medical Pulse Communication: Relapse is a difficult problem
in MCL treatment.
Could you please tell us about the current research progress on relapsed refractory MCLs, especially drug-resistant MCLs after first-line treatment?

MCL is still an incurable disease, and most patients inevitably develop disease progression and recurrence
during follow-up.
Treatment of relapsed/refractory MCL remains challenging, with survival time for patients who relapse after first-line autologous hematopoietic stem cell transplantation being only about
two years.
Patients with advanced relapse demonstrate that the original regimen is effective and lasts longer, so the original regimen can be re-treated; In patients with early relapse, in addition to traditional chemotherapy drugs, BTK inhibitor monotherapy or combination regimens have shown good efficacy and safety
.
However, for patients who progress after treatment with BTK inhibitors, options are currently limited, and the development (monotherapy or combination) of drugs such as non-covalent BTK inhibitors, BCL-2 inhibitors, CD20/CD3 bispecific antibodies, and novel antibody-drug conjugates may provide more treatment options
for patients with relapsed/refractory MCL.

Medical Pulse Pass: What are your expectations and prospects for the exploration of BTK inhibitors, BCL-2 inhibitors, CAR-T and other new drugs and new therapies in MCL?

MCL is the current research hotspot, new drugs emerge in an endless stream, including BTK inhibitors, BCL-2 inhibitors, lenalidomide, PI3K inhibitors, etc.
are being explored
in MCL.
CAR-T is a very effective treatment modality for patients with relapsed/refractory MCL, particularly in patients who have failed treatment with
BTK inhibitors.
The number of CAR-T clinical studies in China ranks first in the world, and many CAR-T studies initiated by researchers have achieved very good efficacy and are an important treatment for
relapse/refractory MCL.
In addition, MCL has many new targets under development, but in general, the efficacy of small molecule targeted drugs monotherapy MCL will not be particularly ideal, and it is easy to produce drug-resistant mutations, so multi-target combination therapy is an important direction
for future exploration.
Bispecific antibodies are in the rapid clinical development stage, and the early efficacy in the MCL cohort is encouraging, comparable to the efficacy of CAR-T cell therapy, and it is also a research direction
worth looking forward to.
With the continuous discovery of new targets, the continuous development of new drugs, and the continuous exploration of new drug combination programs, it is believed that new breakthroughs
will be brought to the treatment of MCL in the near future.

Professor Yi Shuhua

• Doctor of Medicine, Chief Physician, Master Supervisor

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

• National Center for Clinical Medical Research on Blood System Diseases

• He is a member of the 11th Committee of the Hematology Branch of the Chinese Medical Association and the Lymphocyte Disease Group

• He is the sixth member and academic secretary of the Hematology and Oncology Professional Committee of the Chinese Anti-Cancer Association

• Leader of the Chinese Fahrenheit Macroglobulinemia Working Group

• Deputy Leader of the Chinese Follicular Lymphoma Working Group

• He is a member of the Blood Immunology Branch of the Chinese Society of Immunology

• He is a member of the Hematology Group of the Chinese Society of Experimental Hematology

• He is the chairman of the Hematology and Oncology Professional Committee of Tianjin Anti-Cancer Association

• Member of the Lymphoma Professional Committee of Tianjin Anti-Cancer Association

• He is the first member of the Hematology Committee of Tianjin Medical and Health Society

• He is the first member of Tianjin Society of Hematology and Regenerative Medicine

• Youth member of the Professional Committee of Tianjin Association of Integrative Traditional Chinese and Western Medicine

• 2016.
  2-2016.
  9 Visiting Scholar, MD Anderson Cancer Center, USA

• 2016.
  9-2019.
  1 Postdoctoral Fellow, City of Hope National Medical Center, USA

• He has published more than 20 SCI articles and more than 10 reviews as the first author/corresponding author
  .
  As an author, he participated in the formulation of the "China B-cell Chronic Lymphoproliferative Disease Diagnosis Expert Consensus (2014 and 2018 Edition)", the "Chinese Expert Consensus on the Diagnosis and Treatment of Mantle Cell Lymphoma (2016 Edition)" and the "Expert Consensus on the Diagnosis and Treatment of Lymphoma Lymphocyte Lymphoma/Fahrenheit Macroglobulinemia (2016 Edition)"
  .
  He is the deputy editor of 1 treatise and co-editor of
  5 treatises.
  Young Editorial Board Member of "China Oncology Clinic", Corresponding Editorial Board Member of Leukemia and Lymphoma

• He has won 3 National Natural Science Foundation of China, Tianjin Natural Science Foundation, Xiehe Young Teachers Fund and various horizontal funds
  .
  As a backbone, he participated in 5 projects such as the National Science and Technology Support Program, the National Natural Science Foundation of China, and the Innovation Project

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