CCSC: No matter how big or small, CAR-T is used in refractory lymphoma

Chimeric antigen receptor T cell (CAR-T) therapy, as a disruptive innovative therapy, is booming in China
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On June 22, 2021, Yikaida® (Akilunza injection) was officially approved by the National Medical Products Administration (NMPA), becoming China’s first CAR-T therapy drug targeting CD19 for the treatment of relapse/ Adult patients with refractory large B-cell lymphoma (R/R LBCL) bring new treatment options to patients with R/R LBCL
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At present, it has been approved in 38 countries around the world, and has accumulated nearly 5,000 patient experience
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In order to promote the development of China's CAR-T field, build China's CAR-T star treatment center, and cooperate with international and domestic diagnosis and treatment
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"CCSC (China CAR-T Star Center)-Kylinhui International Connection" continues! September 28, 2021-The new phase of Kylin Club International Connection was successfully held
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The conference has the honor to invite Professor Niu Ting from West China Hospital of Sichuan University as the chairperson; Professor Sattva S.
Neelapu from MD Anderson Cancer Center and Professor Ji Jie from West China Hospital of Sichuan University as speakers; Professor Yongqian Jia from West China Hospital of Sichuan University and Wu from West China Hospital of Sichuan University Professor Mat, Professor Zhang Li of West China Hospital of Sichuan University, Professor Ma Hongbing of West China Hospital of Sichuan University, and Professor Xiao Shuai of West China Hospital of Sichuan University as panellists, focusing on cutting-edge topics in the field of CAR-T cell therapy, and commenting on Fosun Kate’s CAR-T cell therapy drugs In-depth discussions and exchanges were conducted on Akirensai injection
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Below, I will take you to review the wonderful links of this conference.
I hope that this conference can expand clinicians' understanding of the clinical efficacy of Akirensai injection and further improve the clinical benefits of patients
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Kirin Assembly-Introduction to the Department of Hematology, West China Hospital of Sichuan University In this session, Professor Ji Jie of West China Hospital of Sichuan University will give a brief introduction to the Department of Hematology of West China Hospital of Sichuan University
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The Department of Hematology, West China Hospital of Sichuan University was formally established in 1986
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In 2008, he was awarded the "Key Clinical Specialty of Sichuan Provincial Department of Health" and was awarded the "National Key Clinical Specialty Construction Project of the Ministry of Health" in 2011
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The Department of Hematology of West China Hospital of Sichuan University ranks among the top ten in many specialties nationwide
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Interpretation of the clinical application of CAR-T in LBCL from an international perspective.
In this session, Professor Sattva S.
Neelapu from MD Anderson Cancer Center shared a speech entitled "Clinical application of CAR-T in LBCL: International perspective"
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Interpretation of the efficacy and safety of CAR-T in the ZUMA-1 study and the real-world study, Professor Sattva S.
Neelapu first introduced the efficacy of Akirensai injection in the ZUMA-1 study
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The ZUMA-1 study is the world's first multicenter study using CD19 CAR-T to treat R/R LBCL
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The results of the study showed that Akirensai injection has excellent efficacy in R/R LBCL patients, with an overall response rate (ORR) of 83% and a complete response (CR) rate of 58%
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At a median follow-up of 27.
1 months, the progression-free survival (PFS) rate of R/R LBCL patients reached 39%, and most of the patients who had no disease progression 6 months after treatment did not have disease recurrence, suggesting that akirenzine injection Liquid may be able to cure some patients
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The updated results of the ZUMA-1 study announced at the 2020 ASH Conference showed that the 4-year overall survival (OS) rate of R/R LBCL patients reached 44%
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Compared with the SCHOLAR-1 study conducted in the pre-CAR-T era, Akirensai injection significantly prolonged the OS of patients with R/R LBCL (2-year OS rate: 50% vs 12%)
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In addition, a subgroup analysis of the ZUMA-1 study showed that compared with R/R LBCL patients with high tumor burden, R/R LBCL patients with low tumor burden had longer duration of remission, and the occurrence of ≥3 grade adverse events (AE) The rate is also lower
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Professor Sattva S.
Neelapu suggested that patients with R/R LBCL should receive Akirensai injection before the disease progresses and the tumor burden increases, in order to obtain better efficacy and safety
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In view of the excellent efficacy of Akirenzine injection in the ZUMA-1 study, the FDA approved Akirenzine injection for the treatment of R/R LBCL in 2017
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Professor Sattva S.
Neelapu then introduced the safety of Akirensai injection in the ZUMA-1 study
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In the ZUMA-1 study, the safety of Akirensai injection in the treatment of R/R LBCL patients is good, and most of the AEs are grade 1-2
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Among them, cytokine release syndrome (CRS) and nervous system toxicity (TN) mainly occur in the early stage of treatment.
The median time of occurrence of CRS is the second day after treatment (range: 1-12), and the median time of occurrence of NT is treatment After the 5th day (range: 1-17)
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In addition to CRS and NT, the treatment of R/R LBCL with akirensai injection will also have some late toxic events.
Some patients have transient aphasia and epilepsy after receiving akirensai injection for 2 months.
The treatment is 0.
5- Hemophilic syndrome (HLH) occurs after 3 months
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About 30% of patients develop ≥ grade 3 cytopenia after 30 days of treatment, which can be managed by the administration of growth factors (granulocyte colony stimulating factor [G-CSF]) and blood transfusion
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Most patients have B-cell aplasia, and some patients have B-cell aplasia that can last for more than one year.
Patients with hypogammaglobulinemia and repeated infections must be given immunoglobulin replacement therapy
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In addition to B cell aplasia, some patients may also experience CD4+ T cell aplasia after receiving Akirensai injection.
Among them, 37% of the patients have CD4+ T cell aplasia for more than 1 year.
This part of the patient needs to be prevented Measures to prevent opportunistic infections
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In addition, injection therapy A Jilun game may also lead to patients with viral hepatitis, including chronic hepatitis B and chronic hepatitis
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Precautions for CAR-T treatment Professor Sattva S.
Neelapu then introduced the precautions for the treatment of Akirensai injection
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For the first attempt to use Akirensai injection to treat R/R LBCL patients, Professor Sattva S.
Neelapu suggested that the enrollment conditions of the ZUMA-1 study should be used to screen suitable treatment patients
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For centers with certain CAR-T treatment experience, the treatment criteria for patients can be appropriately relaxed, including ECOG scores of 2-3 points, previous treatment for central nervous system diseases, previous allogeneic hematopoietic stem cell transplantation, and previous CD19 CAR-T treatment and other patients
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Professor Sattva S.
Neelapu said that advanced age is not completely an obstacle to CAR-T treatment.
MD Anderson Cancer Center has used CAR-T to successfully treat an 85-year-old patient
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Some patients may consider bridging treatment after leukocyte depletion to further control the disease
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However, bridging therapy should not be too aggressive to avoid patients with hemocytopenia or renal dysfunction
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For patients with good disease conditions, consider giving dexamethasone monotherapy or methylprednisolone combined with rituximab bridging therapy; for patients with poor disease conditions (such as double-hit/triple-hit lymphoma), it may be given Bridging therapy of rituximab combined with hyperfractionated cyclophosphamide and dexamethasone (i.
e.
R-HyperCVAD regimen without vincristine and doxorubicin); elderly patients can be given gemcitabine combined with oxaliplatin regimen or Benda The bridging treatment of mustine combined with rituximab; for patients with a single huge mass, local radiotherapy can be used to control the lesion
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All patients should stop using steroids in bridging therapy at least 1 day before lymphoblastic chemotherapy
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After receiving CAR-T cell infusion, patients should observe their physical signs every 4 hours, perform CRS and NT assessment twice a day, and perform daily blood routine, metabolomics, C-reactive protein, and ferritin tests
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G-CSF can be used for patients with neutropenia, but the use of the gene macrophage colony stimulating factor (GM-CSF) that may increase the risk of CRS should be avoided
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Antibacterial drugs such as levetiracetam can be used preventively after CAR-T cell infusion
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Patients with CRS require cardiac monitoring to prevent cardiovascular AEs
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Patients are usually discharged from the hospital 30 days after receiving CAR-T treatment.
If symptoms related to CRS and TN occur after discharge, they should be reported promptly.
Routine blood tests should be performed every 2 weeks within 3 months after discharge, and CD4+T should be performed 1 year after discharge.
Cell, CD8+ T cell, B cell count detection
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When a patient has fever of unknown origin, cytomegalovirus, Epstein-Barr virus, and fungal infections should be tested
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Patients with hemocytopenia and elevated ferritin (>5000ng/mL) should be monitored for HLH after discharge
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In the next part of the discussion session, the participating experts discussed the sharing of Professor Sattva S.
Neelapu
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Professor Jia Yongqian first raised questions about the possibility of the timing of the use of Akirensai injection in advance
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Professor Sattva S.
Neelapu said that some random studies have begun to explore the timing of the use of Akirensai injection
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The ZUMA-7 study compared the efficacy and safety of Akirensai injection and standard second-line treatment of R/R LBCL
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The results of the study show that the second-line treatment of R/R LBCL with akirensai injection can reduce the risk of events (disease progression, new therapies or death) by 60%, while the safety is controllable
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Although the specific results of the study have not yet been announced, akirensai injection has the potential to become the standard second-line therapy for patients with R/R LBCL
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In addition, the ZUMA-12 study explored the efficacy and safety of Akirensai injection in the first-line treatment of high-risk LBCL
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The mid-term results of the study showed that the first-line treatment of high-risk LBCL by akirensai injection also showed excellent efficacy, with an ORR of 85% and a CR rate of 74%.
At a median follow-up of 9.
3 months, 70% of patients continued to remission.
Status
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Professor Sattva S.
Neelapu said that the efficacy and safety of Akirensai injection in the front-line treatment of LBCL are worthy of further exploration, and the prospect of Akirensai injection in the front-line treatment of LBCL is worth looking forward to
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Professor Yongqian Jia then asked about the possibility of combining other drugs during CAR-T treatment to further enhance the efficacy
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Professor Sattva S.
Neelapu said that the combination of immunomodulator lenalidomide and CAR-T is worthy of attention
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Lenalidomide can effectively regulate the tumor microenvironment, and preclinical studies have shown that lenalidomide combined with CAR-T has a good effect
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Some patients who relapsed after CAR-T treatment also got better disease remission after receiving lenalidomide treatment
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A number of studies are currently exploring the efficacy and safety of the combination of related immune drugs and CAR-T, and we look forward to the publication of relevant research results in the future to provide more guidance for the use of the CAR-T combination program
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Professor Niu Ting finally asked whether the early intervention of tocilizumab and steroids would affect the efficacy of Akirensai injection
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Professor Sattva S.
Neelapu said that the subgroup analysis of the ZUMA-1 study showed that the early intervention of tocilizumab for CRS will not affect the efficacy of akirenxie injection, but it may increase the probability of TN, so it is not It is recommended to use tocilizumab prophylactically for all patients, and tocilizumab should be used according to the grade of CRS that occurs in the patient
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Real-world research and analysis results show that the use of steroids may have a certain impact on the efficacy of Akirensai injection
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Professor Sattva S.
Neelapu recommends using the lowest dose of steroids as much as possible for intervention, and at the same time shortening and delaying the intervention time of steroids as much as possible to ensure the efficacy of Akirensai injection
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Summary At the end, Professor Niu Ting made a summary of the meeting
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Professor Niu Ting thanked Professor Sattva S.
Neelapu for his wonderful speech and detailed answers.
Experts have a deeper understanding of the efficacy, safety, and use strategies of CAR-T, and they have learned a lot
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The meeting ended successfully in the heated discussion of experts and scholars! Poke "read the original text", we make progress together