Professor Ke Xiaoyan's team reveals the relationship between the genetic background of patients with relapsed refractory DLBCL and the efficacy of CAR-T: exploring the potential and challenges of CAR-T in the real world

In recent years, in the field of diffuse large B-cell lymphoma (DLBCL), T-cell lymphoma and multiple myeloma (MM), there have been many early clinical studies and post-marketing studies that confirm the efficacy and safety of chimeric antigen receptor T cell (CAR-T) therapy, CAR-T has become a very promising treatment plan, but there are still patients who are ineffective, or even relapse
after a short period of effectiveness.

To further explore the factors that may influence CAR-T treatment, Dr.
Shi Hui, from Professor Kexiaoyan Hu Kai of Beijing Boren Hospital, published an article titled "Genetic landscapes and curative effect of CAR T-cell immunotherapy in relapse and refractory DLBCL" in the journal Blood Advances patients' paper provides a new perspective
for researchers in the specialized field of hematologic lymphoma.

In view of the innovation points of this research, Professor Ke Xiaoyan pointed out that the wide application of second-generation sequencing technology in hematological tumors has been unanimously recognized by everyone, but the difference in the efficacy of CAR-T in patients with different genotypings of R/R DLBCL is not clear
.

Professor Ke Xiaoyan Hu Kai's team summarized and analyzed the second-generation gene sequencing results of tumor tissues of 105 R/R DLBCL patients in our center, aiming to find out the correlation between tumor genes and CAR-T efficacy
.

The study pointed out that the incidence of TP53 mutation in this population was close to 50%, much higher than that in patients with initial treatment of DLBCL, reflecting the adverse prognosis factor of TP53 mutation as R/R DLBL; The molecular characteristics of the other six epigenetic abnormalities are also prominent, with an incidence rate of more than 15%.


Since it is not clear whether cellular immunotherapy (such as CAR-T therapy) can overcome these molecular characteristics of poor prognosis, Dr.
Shi Hui of our team analyzed
the genetic abnormalities and efficacy of patients receiving CAR-T treatment.

The results showed that CAR-T treatment could overcome the poor
prognosis caused by most cytogenetic abnormalities.

Different from previous chemotherapy, the efficacy and prognosis of CAR-T therapy are less affected by the adverse factors of molecular abnormal prognosis, and many patients with molecular abnormalities that are considered to have poor prognosis in the era of chemotherapy still have good efficacy
for CAR-T treatment.

If a patient is found to carry molecular abnormalities in the prognostic phase and does not respond well to chemotherapy, a transition to cellular immunotherapy (e.
g.
, CAR-T therapy) should be done as early as possible, possibly to improve their prognosis
.

However, the efficacy and prognostic effect of TP53 mutations on CAR-T therapy are still controversial, and my team will further explore follow-up treatment options for patients with TP53 mutations
.

Professor Hu Kai pointed out that the Department of Adult Lymphoma of Beijing Boren Hospital has accumulated rich experience in CAR-T treatment in recent years, and with the gradual increase of CAR-T treatment cases in the real world, the clinical problems faced will become more complicated
.

The real-world application experience suggests that CAR-T treatment has high requirements for the patient's immune status, and the multi-line treatment in the early stage may lead to the patient's immune insufficiency, which in turn affects the efficacy of CAR-T, and the treatment line of CAR-T treatment may be moved
forward in the future.

Therefore, choosing the right timing of CAR-T treatment, combining with traditional treatment plans, and exploring personalized, refined, and whole-process management are the main clinical tasks
in the field of hematology and oncology.

Currently, there are two ways to CAR-T cell therapy: (1) join clinical trials; (2) Application of CAR-T products
on the market.

However, many patients are unable to join clinical trials due to enrollment conditions, and the cost of CAR-T products on the market is expensive, and many patients are difficult to afford
.

Therefore, there are not many patients who can receive CAR-T
treatment.

With the vigorous development of domestic CAR-T treatment in the future, it is expected that more CAR-T products will be listed on the market, so that CAR-T treatment can benefit more hematological tumor patients and save more lives and families
.

Professor Ke Xiaoyan

• Chief Physician, Department of Hematology, Peking University Third Hospital, Grade II Professor, PhD supervisor

• Deputy Director of the Department of Hematology, Peking University Health School

• Chief Consultant of Adult Lymphoma Department, Beijing Boren Hospital

• Standing Director of the Chinese Association of Women Physicians

• Chairman of the Targeted Therapy Committee of the Chinese Association of Women Physicians

• Honorary Director of the Hematology Society of the Chinese Association of Women Physicians

• Vice Chairman of the Hematology and Oncology Committee of the Chinese Association for the Elderly

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

• Member of the Standing Committee of the Lymphoma Committee of the Chinese Anti-Cancer Association

• Member of the Oncology Professional Committee of the Beijing Branch of the Chinese Medical Association

• He is a member of the Lymphoma Group of the Chinese Medical Association Hematology Society

• He is a member of many associations such as the Chinese Society of Experimental Hematology

• Associate Editor of Journal of Leukemia Lymphoma, Editorial Board Member of Several Journals

• Ministry of Health, Beijing Municipal Medical Technology Appraisal Consulting Expert

• Central Health Consultation Specialist

Professor Hu Kai

• Chief Physician, M.

  
  

• Integrated diagnosis of lymphogeneous hematopoietic system tumors, standardized therapy, molecular targeted therapy and immunotherapy, hematopoietic stem cell transplantation
  .
  
  He has rich experience in the diagnosis and treatment of recurrent refractory lymphoma and myeloma, and has completed more than 500 cases of CAR-T cell treatment for R/R lymphoma and myeloma
  

• He is a member of the Geriatric Oncology Professional Committee of the Chinese Gerontology Society

• He is an expert member of the municipal "hub-type" social organization of the Beijing Medical Association

• He is a member of the Blood Professional Committee of the Beijing Perioperative Medical Research Association

• Member of the first China T-cell lymphoma working group of the Hematology and Oncology Professional Committee of the Chinese Anti-Cancer Association

• He is a member of the Health Science Popularization Professional Committee of the Chinese Health Management Association

• He is a member of the Hematopoietic Stem Cell Transplantation and Cell Therapy Professional Committee of the Chinese Medical Education Association

• He is a member of the Clinical Research Committee of Beijing Cancer Association

• Young member of the Blood Committee of Beijing Medical Association

• Participated in more than 20 international and domestic multi-center clinical studies; The first author and corresponding author have published more than 30 papers in Chinese and English; Edited and translated 5 books; He has reported the team's research results
  at many domestic and foreign academic conferences (American Hematology Annual Conference, European Hematology Annual Conference).
  
  

Dr.
Shi Hui

• M.
  D.
  , Attending Physician of Adult Lymphoma/Myeloma Department of Beijing Gaobo Boren Hospital, Ph.
  D.
  candidate, Institute of Hematology, Chinese Academy of Medical Sciences-Peking Union Medical College, Visiting Scholar
  of Biochemistry and Molecular Biology, University of Miami.
  
  Engaged in targeted therapy for lymphoma, immunotherapy including CART cell therapy, and hematopoietic stem cell transplantation
  for blood diseases.
  
  Participated in more than 20 international and domestic multi-center clinical studies; The first author and corresponding author have published more than 10 papers in Chinese and English; He has spoken at many academic conferences at home and abroad (American Hematology Annual Conference, European Hematology Annual Conference).
  

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