The first case in Central and South China, Akilunza CAR-T treatment of R/R DLBCL patients achieved complete remission, and China's efficacy has been verified again

Wuhan Tongji Hospital, as the first batch of centers with CAR-T qualifications in the country, under the leadership of Professor Zhou Jianfeng, on September 30, 2021, the evaluation of the efficacy of the first patient using commercial CAR-T Akilunza treatment in Central and South China was completed.
Ease
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Next, let us come to the clinical frontline of the Department of Hematology of Wuhan Tongji Hospital together, and ask Professor Zhou Jianfeng and his treatment team to introduce the specific treatment process of the patient and share the full management experience of CAR-T treatment
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Professor Xiao Yi is in line with international standards, and the curative effect in China has been verified again, and the cure of R/R DLBCL can be expected! Could you please introduce the treatment of the first patient in Central and South China who was treated with commercial CAR-T Akirensai and achieved complete remission and was discharged smoothly? How do you feel about cooperating with Fosun Kate during the treatment process? Professor Xiao Yi The patient is a refractory Non-GCB R/R DLBCL patient with P53 mutation, and the disease has progressed with poor efficacy after receiving multi-line chemotherapy
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After the patient was admitted to the hospital, a precise bridging treatment was selected based on various evaluation indicators, molecular genetic characteristics and our previous treatment experience
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After the patient was subsequently treated with Akirensai CAR-T, only minor adverse reactions occurred: cytokine release syndrome (CRS) was grade 1, no neurological event (NE) occurred, and it was relieved after symptomatic treatment
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Fosun Kate's products are not only very effective, but also the service process is clear and smooth.
During the treatment of the patients, the staff gave the patients extremely warm care
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Most importantly, after CAR-T treatment, the patient has not progressed in the past two months, and the assessment results of PET-CT and liquid biopsy show that the patient has reached complete remission (CR)
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Could you please talk about the advantages of CAR-T therapy compared with traditional therapy? How to choose the timing of CAR-T treatment to maximize the benefit of patients? Professor Xiao Yi CAR-T is an epoch-making drug, a living drug that is different from traditional radiotherapy, chemotherapy and other therapies
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Both clinical practice and clinical trial results show that the ORR of CAR-T therapy is between 70%-80%, and the CR rate is 40%-50%
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In the past, some R/R DLBCL patients were almost on the verge of extinction, but after using CAR-T therapy, they have obtained long-term disease control and even cure effects
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At present, the follow-up time of Achilles is the longest in CAR-T, and the patient's 4-year overall survival (OS) rate has reached 44%
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To evaluate the timing of the use of CAR-T therapy, the patient's disease situation needs to be evaluated first
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According to the experience of previous clinical practice, patients with large tumor burden, high lactate dehydrogenase, multi-site infiltration, extranodal disease, poor physical status, and lymphoma in special locations (such as the central nervous system, breast, testis, etc.
) should be treated with traditional therapies The results are not satisfactory, so these patients should start CAR-T treatment as soon as possible
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After multi-line treatment, the patient's physical status is poor, and the tumor burden is large, which affects the curative effect of CAR-T therapy to a certain extent
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Based on the ZUMA-12 research results and years of CAR-T treatment experience, I believe that starting CAR-T treatment as soon as possible within the indications and gradually promoting the number of CAR-T treatment lines may be an effective choice in the future
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Regarding the management of adverse reactions during CAR-T treatment, what suggestions do you have? Professor Xiao Yi's CD28 costimulatory domain CAR-T is generally safe and controllable, with mild adverse reactions
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CAR-T treatment-related adverse reactions such as CRS, often manifested as fever, blood pressure drop, hypoxemia, etc.
; CAR-T cell-related encephalopathy syndrome (CRES) often manifested as loss of consciousness, convulsions, aphasia, and inability to move
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The occurrence of serious adverse reactions will affect the survival of patients and the efficacy of CAR-T, so it is necessary to monitor and control the occurrence of adverse reactions as much as possible during the treatment process
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First of all, before CAR-T infusion, accurate bridging treatment should be performed according to the patient's disease condition, which not only allows the patient's own vitality to be preserved, but also reduces the patient's tumor burden
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After CAR-T infusion, the patient's blood pressure, oxygen saturation, and body temperature should be closely monitored, and the patient's mental condition should be evaluated daily
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If a patient develops CRS or CRES during CAR-T treatment, it is necessary to choose drugs such as tocilizumab or glucocorticoid for treatment according to the severity of the adverse reaction
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In addition, the monitoring of infection after CAR-T treatment is also very important, including the monitoring and control of viruses, fungi, and bacteria, which also contributes to the long-term survival of patients
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Could you please talk about what aspects of the whole process management of CAR-T treatment include? Regarding the entire management of CAR-T treatment, what suggestions do you have? Professor Xiao Yi's management of CAR-T therapy is a systematic project.
After a patient goes to the hospital, he first needs to evaluate his physical condition, the function of various important organs, and the previous treatment plan
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At the same time, it is also necessary to evaluate the patient's immune function, including the evaluation of cell viability, uncoating ability, cell killing function, and whether there are congenital immunodeficiency genes
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On the basis of the results of various assessments, accurate bridging treatments are carried out to minimize the patient's tumor burden
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After CAR-T cell reinfusion, it is necessary to closely monitor the occurrence of adverse reactions such as CRS and CRES in patients
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For some chronic problems, such as blood loss, infection and other problems, it is necessary to pay attention to and follow up closely
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In the entire CAR-T treatment process, we are not alone.
We need to cooperate with elites such as ICU, nephrology, cardiovascular, laboratory, and pharmacy teachers for diagnosis and treatment
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In addition, I think we should be doctors with warmth.
They can care for patients even after they are discharged from the hospital, provide timely solutions to problems, and notify patients to go to the hospital for treatment and follow-up.
These are very important safeguards
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Fosun Kate also did a lot of work in the early stage and cooperated with the hospital to carry out personnel training and certification, which effectively guaranteed the safe and effective CAR-T treatment in the hospital
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Could you please talk about the significance of bridging therapy for patients who are planning to undergo CAR-T therapy? Regarding the specific practice of CAR-T therapy in the real world, what suggestions do you have? Professor Xiao Yi’s CAR-T therapy is closely related to the patient’s tumor burden.
The larger the patient’s tumor burden, the worse the physical functioning state, and the greater the risk of subsequent CAR-T therapy.
Based on these factors, I It is believed that the tumor burden should be minimized before CAR-T infusion, and this process is bridging therapy
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In the selection of drugs for bridging therapy, fully understand the patients' past medications and try to choose the drugs that are suitable for the patients; in principle, high-efficiency and low-toxic drugs should be selected; drugs should be selected according to the characteristics of the disease, using molecular genetics and other means to achieve "precision strike"
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Regarding how to use commercial CAR-T products in clinical practice, I have the following suggestions: understand the characteristics of each CAR-T product, understand the efficacy of the product and the incidence and extent of adverse reactions based on clinical trial data; pay attention to CAR -T treatment is managed throughout the whole process to grasp the patient's overall physical condition; more literature study and clinical experience accumulation, the combination of theory and practice is conducive to better use of CAR-T products and bring the greatest clinical benefit to patients
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Head nurse Yuan Hongyan Akilunza CAR-T treatment of R/R DLBCL patients, the adverse reactions are mild and controllable.
Combining the previous CAR-T nursing experience, please talk about the management of AE during CAR-T treatment.
What are the precautions? The head nurse Yuan Hongyan monitors the vital signs of patients during CRA-T infusion
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Starting from CAR-T infusion, patients need to be monitored for ECG for at least 24 hours, and other vital signs, such as body temperature, blood oxygen saturation, blood pressure, etc.
, need to be monitored at the same time
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During CAR-T treatment, it is also necessary to regularly monitor the patient's various cytokine indicators, including blood biochemistry, blood routine, and lentivirus copy number
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During CAR-T treatment, tocilizumab and other drugs must be prepared in advance in the ward.
If the patient has a serious adverse event such as CRS, it can be treated symptomatically in time
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Please talk about the daily care of patients treated with CAR-T after discharge.
What are the precautions? After the head nurse Yuan Hongyan is discharged from the hospital, the following points need to be noted: First, the need to prevent infection
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Due to the current epidemic period, patients must wear masks when traveling and carry disinfectant wipes with them
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The patient stays at home, and the room needs to be ventilated for more than half an hour in the morning and evening
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Patients should try to avoid going out, especially in crowded places
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Second, patients need to follow the doctor's instructions for regular review, especially blood biochemistry and other blood indicators, which are closely related to the evaluation of the safety and efficacy of the patient's treatment
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Regular check-ups help doctors understand the patient's condition and formulate follow-up treatment plans
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Third, try not to drive for two months after the patient is discharged from the hospital
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Since these patients are prone to delayed neurotoxicity, driving and high-risk sports should be minimized
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Fourth, the patient is recommended to live near the hospital within three months after discharge, and it is best to arrive at the hospital for treatment within 60 minutes.
If an adverse event occurs, it is convenient for the doctor to deal with it in time
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Fifth, it is recommended that patients fix a long-term escort for daily care and companionship
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Professor Zhou Jianfeng's comments and conclusions 1.
Patients with refractory DLBCL such as P53 mutations have different responses to traditional treatment options, and most patients have a poor prognosis.
In contrast, CAR-T therapy is more effective and can be given priority in treatment
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The timing of CAR-T treatment is very important.
If the patient's physical condition allows, the earlier CAR-T treatment is carried out, the greater the possibility of benefit
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2.
The safety of akirenzal is good, and the adverse reactions are manageable and controllable.
For severe adverse reactions such as CRS, tocilizumab and hormone therapy are usually used clinically
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ZUMA-1's cohort 4 and cohort 6 studies have shown that early use of low-dose hormones can significantly reduce the incidence of adverse events without affecting the efficacy
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The first patient in Wuhan Tongji Hospital who received CAR-T treatment had only minor adverse reactions after cell infusion, which was controlled in time by symptomatic treatment
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It can be seen that the CD28 costimulatory CAR-T product has a good curative effect and is safe and controllable.
This is not only the result of clinical research, but has also been verified in real-world applications in China
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3.
Bridging therapy can reduce tumor burden and help patients prepare for reinfusion.
It is a very important link in the full-process management of real-world CAR-T therapy
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Especially for patients with rapid disease progression and high tumor burden, bridging therapy is essential to reduce toxicity, improve efficacy, and delay disease progression
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4.
The safety management of CAR-T treatment is inseparable from the rich clinical experience of the medical team
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Identifying adverse reactions as early as possible and adopting an effective treatment plan is the key to ensuring the efficacy and safety of CAR-T
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In addition, the development of MDT will also help the treatment team have a deeper and more comprehensive understanding of the patient's condition and escort the entire management of CAR-T treatment
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Professor Zhou Jianfeng, Chief Physician, Doctoral Supervisor, Huazhong Scholars, Leading Talents Distinguished Professor, National Outstanding Youth Fund Winner, Director of the Department of Hematology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Deputy Director of the Department of Internal Medicine, Director of the Clinical Research Center of Tongji Hospital, Hubei Provincial Blood Director of the Immune Cell Therapy Clinical Research Center Member of the Standing Committee of the Blood Branch of the Chinese Medical Association Chairman of the Hematology Branch of the Chinese Anti-Cancer Association Deputy Chairman of the Hematological Oncology Committee of the Chinese Association of Chinese and Western Medicine Vice Chairman of the Chinese Anti-Leukemia Alliance Vice Chairman of the Oncology Branch of the Chinese Medical Association Translational Medicine Group Deputy team leader Chinese Journal of Hematology and other academic journals and other academic journals and other academic journals and other major clinical professional directions are molecular diagnosis, molecular therapy and cellular immunotherapy of leukemia, lymphoma and other hematological tumors
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More than 100 professional papers have been published in international journals such as Nature Genetics, J Exp Med, Cell Research, Blood, JACI, JNCI, and leukemia
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Professor Xiao Yi, Department of Hematology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Doctor of Medicine, Chief Physician, Doctoral Supervisor, Visiting Scholar, Bone Marrow Transplant Center, University of Hamburg, Germany, Standing Committee Member, Hubei Branch of the Chinese Bone Marrow Bank, Standing Committee Member, Chinese Society of Geriatric Hematology, China Hematopoiesis Member of the Standing Committee of Stem Cell Transplantation and Cell Therapy Professional Committee Member of the Leukemia Professional Committee of China Medical Education Association Director of the Expert Committee of the Academic Branch (Hubei) Yuan Hongyan, Head Nurse, Head Nurse, Master's Degree, Chief Nurse, Party Member of the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Member of the Evidence-Based Group of the Nursing Department of Tongji Hospital Member of the Scientific Research Innovation Team of Tongji Hospital One of the 2013 and 2014 internal medicine teaching general tutors won the 2013-2014, 2014-2015 "excellent general tutoring" and won the 2018 Tongji Hospital advanced labor union workers to write 8 papers; actively participated in the declaration of various topics in the hospital, presided over Tongji A hospital youth project, with the second author participating in a research interest and direction: leukemia symptom group management, CAR-T full-course management, and refined management of oral mucositis (OM) in chemotherapy patients.
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