2022CSH Professor Huang Liang: Based on the needs, the exploration continues, and the future development trend of double-strike and double-expression lymphoma diagnosis and treatment is expected according to the current status of diagnosis and treatment

Diffuse large B-cell lymphoma (DLBCL) has become one of the malignant tumors whose incidence is increasing year by year, and double-strike and double-expressed lymphoma belong to the special subtypes of DLBCL, with poor clinical prognosis, and the development of diagnosis and treatment has attracted clinical attention
.
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 Huang Liang of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology was invited to share his views and thoughts
on the progress, challenges and future development of DLBCL field.

DLBCL is the most common B-cell lymphoma, please talk about the current progress in the diagnosis and treatment of DLBCL? What are the unmet clinical needs in terms of prognosis?

In recent years, the field of DLBCL has made rapid progress in immunotherapy, and many antibody drugs, CAR-T therapies have emerged, and the treatment status has been significantly improved
.
In terms of antibody drugs, there are monoclonal antibody Tafasitamab targeting CD19, bispecific antibody Mosunetuzumab targeting CD20×CD3, and ADC drug Polatuzumab Vedotin targeting CD79b, etc.
, which have achieved good efficacy in the field of DLBCL, and some patients have achieved sustained remission
。 In terms of chimeric antigen receptor (CAR)-T cell therapy, two CD19-targeting CAR-T products have been listed in China, and their efficacy is obvious to all, in
addition to the research on new CAR-T therapies such as CAR-T and bispecific CAR-T targeting CD20 or CD22 is also underway.
Our center is currently exploring the direction of CAR-T combined autologous hematopoietic stem cell transplantation and insertion of CD19 CAR sequences at PD-1 gene loci, and looks forward to breakthroughs in the
future.

Traditional International Prognostic Index (IPI) scoring systems are now increasingly unable to meet the increasing clinical demand
.
The system alone cannot distinguish some high-risk patients from low- and medium-risk patients, some low-risk patients do not have good results with standard induction chemotherapy, and some high-risk patients achieve long-term survival
.
In order to improve this situation, the clinical prognosis assessment, especially in the screening of high-risk patients, is currently undergoing multi-directional exploration, including assessment of cell origin, detection of double-expression and double-strike lymphoma, second-generation sequencing (NGS), monitoring of minimal residual disease (MRD), etc.
, the results are to be seen
.

Medical Pulse Pass: What is the current status of the prognostic evaluation system for double-strike and double-expression lymphoma? What are the shortcomings of the system at present?

There is currently no uniform prognostic evaluation system for double-strike and double-expression lymphoma, and such patients are often considered to have a poor
prognosis due to advanced age, high IPI score, late clinical stage, and combined extranodular organ involvement.
At present, some studies are exploring the prognostic relationship between high expression of BCL-2 and such tumors, but the overall lack of multicenter, prospective studies confirms that further exploration
in this field is needed in the future.

I think it is important to evaluate the prognosis
of patients with double-strike and double-expressing lymphoma through efficacy indicators.
If the patient develops drug resistance or poor outcomes after treatment, the prognosis is often poor; If remission is sustained, the prognosis is usually better
.
For patients in persistent remission, hematopoietic stem cell transplantation may be considered
.

Medical Pulse Pass: What other treatment options in the field of DLBCL are worth exploring? Can you please look forward to the prospect of double strike and double expression lymphoma?

In addition to the immunotherapy drugs mentioned, small molecule targeted drugs are also very worthy of clinical attention
.
The single-agent treatment of such drugs is often not effective, and the combination of drugs is a popular direction, and the clinic can select the corresponding small molecule targeted drugs for specific tumor subtypes, such as the team of Professor Zhao Weiying of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine is carrying out clinical trials
of R-CHOP+X regimen for the treatment of related tumors.

In the field of double-strike and double-expression lymphoma, CAR-T cells have demonstrated good efficacy
in patients with high-risk DLBCL.
The ZUMA-12 study included 40 high-risk DLBCL patients receiving CD19 CAR-T cell therapy (patients with double- or triple-strike lymphoma, n=16), and the results showed that in 37 patients with an overall response rate (ORR) of 89% and a complete response (CR) rate of 78%; Many centers in China are trying HDAC inhibitors combined with immunochemotherapy programs, and have made some progress, and look forward to breakthrough results in the future to benefit many patients
.

With the continuous improvement of medical level, the overall condition of DLBCL has been significantly improved, but focusing on the difficult points, DLBCL, especially the special subtypes such as double-expression and double-strike lymphoma, still need to be explored in many areas such as prognosis stratification and treatment, and the clinic should further refine stratification on the existing basis, actively explore diversified combination treatment strategies, and bring survival benefits
to more DLBCL patients.

Professor Huang Liang

• Ph.
  D.
  , Associate Professor, Deputy Chief Physician, Master Supervisor

• Deputy Director of the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Secretary of the Branch

• Specialty: lymphoproliferative diseases and their immunotherapy

• Visiting Scholar, City of Hope National Medical Center, USA

• He is a member of the Lymphocyte Disease Group and the Youth Committee of the Blood Branch of the Chinese Medical Association

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

• Member and Secretary of Hematology and Oncology Professional Committee of Hubei Anti-Cancer Association

• Vice Chairman of the Youth Committee of the Hematology Branch of Wuhan Medical Association

• He has published nearly twenty SCI papers as the first or corresponding author in journals such as Blood, Cell Research, and Blood Cancer Journal

• He presided over the National Natural Science Foundation of China Youth Project, the Surface Project and the 863 Young Scientist Project of the Ministry of Science and Technology

• Received the 2019 Central China Outstanding Scholars Program Morningstar Gang, the 2019 ASCO and 2018 ASH Abstract Merit Awards, and the MMAAP Foundation Hematology Fellowship Award

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