Ruijin Hospital Mi Jianqing and Xu Jieyou talked about CAR-T diagnosis and treatment experience

With the aging population in China, the incidence of multi -bone marrowoma (MM) in my country is on the rise, and its mortality rate is also high. In recent years, although protease inhibitors, immune regulatory drugs and autologous stem cell transplantation and other new drugs have improved the survival of MM patients, almost all MM patients will relapse, and the treatment plan for recurrence/refractory (R/R) mm will be Limited, the patient's prognosis is poor, and a new solution strategy is urgently needed clinically.

Fortunately, the advent of chimeric antigen receptor T (CAR-T) cell therapy brings the dawn of hope for patients with R/R MM. As early as 2017, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine used BCMA CAR-T products in clinical trials to treat a patient with R/R MM. The patient has achieved clinical cure for 5 years.

"Medicine" invited Professor Mi Jianqing, Professor Mi Jianqing and the attending physician affiliated to the Shanghai Jiaotong University School of Medicine College, to share with CAR-T treatment related management experience, and the clinical value of Car-T therapy and its application prospects in MM patients Looking forward.

New mechanism, unique advantages

CAR-T therapy brings dawn to the treatment of multiple osteoma

Professor Mi Jianqing first introduced: "Multiple osteoma (MM) is the second largest blood system malignant tumor. So far, it is still irreplaceable. Its main symptoms are easily confused with other diseases, including renal function, pathological fractures, severe anemia, and anemia. Hypermalmia, etc., further increased the difficulty of diagnosis and treatment. Patients often came to the blood department after consultation in multiple departments. At the same time, patients with MM patients prone to disease progress after treatment, and patients have poor prognosis. There is an urgent need.

The advent of CAR-T therapy is a major event in the history of human tumor treatment, and it also brings dawn to patients such as MM and other blood tumors. As far as its particularity is concerned, CAR-T therapy breaks the traditional model of tumor treatment, transforms traditional chemistry and biological drugs into drugs for living cells, and is different from previous non-specific transient cell therapy. CAR- In addition to life and specific cell therapy, T cells have laid the foundation for its significant curative effects. "

Figure 1. Professor Mi Jianqing of Ruijin Hospital

Dr. Xu Jie added: "CAR-T therapy has three major advantages and characteristics. First, CAR-T cells belong to 'living drugs'. As long as patients are injected in one dose, they can have a continuous anti -tumor effect, and traditional anti -tumor treatment requires multiple consolidation treatment.

Second, CAR-T therapy is mainly aimed at the receptor protein on the surface of the cell membrane, which can overcome some of the genetic mutations of tumor cells, including genetic mutations and chromosomal variations. Due to the heterogeneity of the tumor, there may be tumor cloning with different mutations in the patient's body, and CAR-T cells can track the common marking of tumor cells, and the cancer cells are exhausted '. It can target 1 ~ 3 different tumor antigens at the same time, which can well overcome the heterogeneity of tumor.

Third, CAR-T therapy, as a new type of cellular immunotherapy, is a anticancer that is more in line with natural laws compared to the original traditional treatment. The T lymphocytes in normal human body play the role of immune surveillance and immune removal, while CAR-T therapy can mobilize T cells to crack down on tumors, which has a small impact on normal cells. "

Figure 2. Dr. Xu Jie, Ruijin Hospital

Based on the advantages of CAR-T therapy, Professor Mi Jianqing talked: "The advantages of CAR-T therapy in the field of hematological tumors are more obvious. Unlike physical tumors, the tumor cells of blood tumors are spread throughout the patient's blood, bone marrow, and corresponding lymph organs. Among them, it is easy to connect with CAR-T cells 'short soldiers'. Therefore, the effect of CAR-T therapy to treat blood tumors is very significant. It has obtained very good in acute lymphocytic leukemia, B-cell lymphoma, MM and other blood tumors. Effective. "

Clinical cure for five years,

The "MAY Plan" witnessed the progress of the doctor's experience and the beneficiaries of the patient's survival. Experience has achieved clinical cure among some patients. Although MM is still an irreparable disease, it is based on targeted therapy such as a combination of CAR-T therapy with immune regulators, protease inhibitors, and comprehensive use of traditional chemotherapy. Camping on tumor cells at all angles may really remove tumor cells, even including tumor stem cells, thereby achieving the possibility of cure.

As early as 2017, Ruijin Hospital used CAR-T products to treat a case of R/R MM patients in clinical experiments. Ms. Ma was diagnosed in 2011 and recurred after multi-line treatment. Then he received CAR-T treatment at Ruijin Hospital in 2017. "Ms. Ma was the first patient in our blood department for CAR-T therapy. She also herself. Once a clinician, with the spirit of "dedication to medical care", it officially opened the door to CAR-T therapy.

For Ms. Ma's entire treatment process, it can be described as "swimming in the swimming middle school". During the treatment, our blood doctor also accumulated valuable CAR-T the practice experience of CAR-T, and gradually learned about the key points of CAR-T therapy, including efficacy assessment, adverse reactions monitoring, follow-up after treatment, etc., to clinicians, and to clinicians. It is also an excellent learning process. "

Regarding CAR-T the treatment related experience, Dr. Xu Jie introduced: "In recent years, our curative effect on CAR-T treatment has grown out a clear methodology. The purpose of short-term and long-term assessment has been different. Long -term evaluation is to evaluate the efficacy on the basis of security.

In short -term security assessment, we are most concerned about cytokine release syndrome (CRS). Usually, CRS is excessive, but it may be extended or lagging in some patients, or it may occur. The degree of response is severe. At this time, the medical team needs to conduct closely monitoring patients, including physiological indicators and vital signs monitoring; the focus in long -term safety assessment is different. Bacterial infections. Timely discovery and early symptomatic treatment is the direct goal of safety assessment.

On the basis of security, the assessment of long -term efficacy is equally important. We will comprehensively evaluate it based on the patient's condition, including serotics, bone marrow, and imaging evaluation. As far as the frequency of evaluation is concerned, it usually evaluates once a month within 3 months after the return, once every 3 months during 3-12 months, and once every 6 months of 12 months, and follow -up It will be carried out for a long time. "

Professor Mi Jianqing and Dr. Xu Jie introduced: "Ms. Ma, as the first patient with R/R MM treatment for CAR-T therapy, has successfully achieved clinical cure. In order to celebrate Ms. Ma obtaining 'rebirth', we specially invited Ma Ma The ladies went to the hospital to visit and held the second celebration for her, named the 'May Program'. The special name has a three -high meaning behind this special name -first, 'May' is a short name for Ms. Ma's English name; second, Ms. Ma was treated in May 2017, and has achieved clinical cure for 5 years in May 2017. Third, May is the season when spring is full of spring and flowers. Beauty and hope to pass to more patients. "

Figure 3. CAR-T Expert Team of Ruijin Hospital

Four -year patients

The effect of BCMA CAR-T has a significant effect, and the future can be expected

Regarding the story behind clinical trials, Professor Mi Jianqing recalled: "Ruijin Hospital carried out the CAR-T clinical study of Legend-2, which has its own inevitability. Related studies are in full swing. For example, Emily Whitehead, which are very familiar with doctors and patients, is the first patient in the world to receive CAR-T therapy and obtain successful leukemia patients. T therapy has also begun to explore in the fields of chronic lymphocytic leukemia, lymphoma, osteoma and other fields. At that time, our hospital paid great attention to Car-T therapy and received strong support from Academician Chen Zhu and Academician Chen Saijuan. Shortly after the successful development of BCMA CAR-T products, the company contacted our hospital and hoped to cooperate with related clinical research. Academician Chen Zhu was based on insights on the development trend of cell therapy and the understanding and recognition of the product. In concept, we recommend that we have bold attempts. Under the concern of Academician Chen Zhu, this BCMA CAR-T clinical study has started rapidly and progress is smooth, saving many patients with blood tumors, including Ms. Ma who has achieved clinical cure for 5 years. "

Regarding the CAR-T product used by Ms. Ma's treatment, Dr. Xu Jie introduced: "This CAR-T product-targeted BCMA product independently developed by the legendary creature contains two anti-BCMA single-domain antibodies It aims to increase its comprehensive ability to target cancer cells. "

Dr. Xu Jie added: "The clinical trials carried out by our hospital showed that in terms of short-term efficacy, most of the patients who received this BCMA CAR-T therapy could get part of the relief state of alleviating from 3 months after treatment. . In terms of long-term efficacy, many patients who have been treated can achieve long-term disease-free survival. According to the result of 4 years of follow-up, the patient's median survival has not yet achieved. Therefore Some patients have received real long-term benefits. "Recently, the international professional academic journal" Journal of Hematology & Oncology "published a paper in cooperation with Legend-2 project researchers such as Professor He Eli, Professor He Ali Eli, Xi'an Jiaotong University Second Academy. A comprehensive and detailed statistical analysis of the four years of follow-up of the four research centers in China carried out LEGEND-2 clinical research was conducted. This is the longest follow-up of BCMA CAR-T for the treatment of R/R MM. The follow-up data for 4 years is encouraging and exciting.

At the end of the interview, Professor Mi Jianqing said: "The CAR-T product of the legendary creature Sidaki Lenys has been included in the breakthrough therapy catalog by the State Drug Administration. In the future, we can be listed in China to further benefit more patients. "

Expert Introduction

Professor Mi Jianqing

Chief physician, professor, doctoral supervisor

Deputy Director of Hematology Department of Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine

Director of the Hematology Center of the Party Branch of Shanghai Hematology Research Institute

Chairman of the Blood Medicine Transformation Professional Committee of the Shanghai Medical Industry Association

Director of the Shanghai Anti -Cancer Association, Deputy Chairman of the Hematology Tumor Sub -Association

Member of the Hematology Branch of the Chinese Medical Association

Member of the Shanghai Medical Association Hematology Specialist Branch

Executive Member of the China Anti -Cancer Association Blood Transformation Medical Professional Committee

Standing Committee of the Blood Branch of the Chinese Medical Association

Member of the Blood Tumor Professional Committee of the China Anti -Cancer Association

Chairman of the Hematology Expert Committee of the China Junior Health Care Foundation

Asia -Pacific Medical Biological Immune Society Blood Branch Chairman of the Blood Branch

Members of Asian Osmisotoma Working Group

Appraisal Expert of the Department of Health Clinical Classification Technical Review Expert Committee

Shanghai Pujiang Talent, Shanghai Leader, Shanghai Excellent Discipline Leader

Expert Introduction

Dr. Xu Jie

Doctor of Medicine, Little Internal Medicine of Ruijin Hospital, Chief Physician and Associate Researcher

Visiting scholar at the University of Pennsylvania Cell Therapy Center

Top ten young people at Ruijin Hospital

Shanghai Excellent Medical Young Talent

Shanghai Outstanding Young Physician

Shanghai Youth Science and Technology Qixing Star

Jiulong Medical Outstanding Young Talent

references:

[1]. Liu j, et al.j hematol oncol. 2019 DEC 10; 12 (1): 136.

[2] In case of Ke Jian. Research on Tumor Prevention, 2019, No. 46, No. 9.

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