CCSC: Rising to the challenge, the application of CAR-T in the treatment of 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 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 25, 2021-The new phase of Kylin Club International Connection was successfully held
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Professor Yang Haiyan from the Cancer Hospital of the University of Chinese Academy of Sciences was invited to host this conference; Professor Robin from King’s College Hospital London, Professor Li Cong from the Cancer Hospital of the University of Chinese Academy of Sciences, and Professor Chen Xi from the Cancer Hospital of the University of Chinese Academy of Sciences as speakers; University of Chinese Academy of Sciences Professor Wu Meijuan from the Affiliated Cancer Hospital, Professor Lei Tao from the Cancer Hospital of the Chinese Academy of Sciences, Professor Yu Haifeng from the Cancer Hospital of the Chinese Academy of Sciences, Professor Peng Shuailing from the Cancer Hospital of the University of Chinese Academy of Sciences, Professor Han Shuiyun from the Cancer Hospital of the Chinese Academy of Sciences, and many top domestic experts As a guest of discussion, focus on cutting-edge topics in the field of CAR-T cell therapy, and conduct in-depth discussions and exchanges on Fosun Kate's CAR-T cell therapy drug 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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The application of CAR-T therapy in patients with refractory DLBCL based on real world data.
In this session, Professor Robin from King’s College Hospital in London shared a speech entitled "Yescarta for Relapsed DLBCL: Real World Experience and lessons learnt"
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Professor Robin first introduced the background of the real-world study of Akirensai injection and the basic information of the patients enrolled in King's College Hospital, London, England.
The proportion of diffuse large B-cell lymphoma (DLBCL) among the enrolled patients was 67%; The median age is 56 years, and the proportion of patients ≥65 years is 21%; the proportion of patients refractory to chemotherapy is 48%; the proportion of patients who have relapsed after receiving transplantation is 25%
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In real-world studies, most of the enrolled patients underwent bridging therapy before receiving CAR-T infusion, but they needed to stop chemotherapy/radiotherapy two weeks before collecting T cells using leukocyte ablation, and stop using steroids one week before
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Common toxic reactions of CAR-T treatment include cytokine release syndrome (CRS), immune effector cell-related neurotoxicity syndrome (ICANS), etc.
At present, these toxic reactions are controllable and can be relieved to a certain extent through treatment
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In the real world study, the median follow-up time was 13.
1 months, the median overall survival (OS) was not reached, and the best overall response rate (ORR) was 83%, compared with the ORR of the ZUMA-1 study (82%) , No significant difference
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The incidence of ≥3 grade CRS was 11%, and the incidence of ≥3 grade ICANS was 17%, which were lower than the results in the ZUMA-1 study (≥3 grade CRS incidence was 13%, ≥3 grade ICANS incidence was 28% )
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CRS usually occurs in most patients around 4 days after CAR-T infusion, ICANS usually occurs around 5 days after infusion, and most patients are treated with tocilizumab usually 1 day or 4 days after infusion
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At present, Akirensai injection is suitable for patients with refractory or relapsed LBCL after second-line chemotherapy or transplantation treatment
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When screening patients before CAR-T treatment, you can consider good physical status, such as patients with a score of 0-1 by the Eastern Cooperative Oncology Group (ECOG), patients without (suspected) virus infection, and patients with good organ function
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Finally, Professor Robin shared two DLBCL cases and elaborated on the treatment process and precautions of patients using Akirensai injection
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Case Sharing The clinical practice of CAR-T therapy in double-strike DLBCL patients In this session, Professor Li Cong from the Affiliated Tumor Hospital of the Chinese Academy of Sciences shared a case of double-strike DLBCL
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The patient is a 68-year-old male with non-GCB type DLBCL.
The genetic test results showed CD19 (15%+), BCL-2 (+, 90%), BCL-6 (+, 60%), C -MYC (+, 50%), Ki-67 (+, 40%-60%); MYC rearrangement, BCL-2 rearrangement
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After perfecting other examinations, it was diagnosed as non-GCB type double-expression double-hit IVA stage DLBCL, and the international prognostic score (IPI) of lymphoma was 5 points
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The patient was previously treated with the R-CHOP regimen (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone)
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After 13 months of complete remission (CR), the patient progressed .

After receiving CD22 CAR-T treatment, the examination results after 1 month showed high-grade large B-cell lymphoma with C-MYC rearrangement, BCL-2 rearrangement, and CD19(+)
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The patient subsequently took lenalidomide 25 mg qd and programmed death receptor-1 (PD-1) 200 mg once.
One month later, PET-CT examination showed disease progression
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At present, the patient has completed apheresis, and then undergoes CD19 CAR-T cell infusion
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After Professor Li Cong's case sharing, the Chinese and foreign parties discussed relevant issues involved in the case
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For patients with poor tolerance after multi-line chemotherapy, Professor Robin believes that the collection of peripheral blood stem cells is not necessary
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In addition, Professor Robin mentioned that currently LBCL patients in the UK can only receive one CAR-T treatment.
In the case, this patient received CD22 CAR-T treatment and then received CD19 CAR-T treatment.
There is no clinical experience in the UK
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Case Sharing Application of CAR-T Therapy in Patients with Refractory DLBCL In this session, Professor Chen Xi from the Cancer Hospital of the University of Chinese Academy of Sciences shared a case of refractory DLBCL
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The patient was a 52-year-old female with non-GCB DLBCL, with an ECOG score of 1, and genetic examination results showed BCL-6 rearrangement and TP53 deletion
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The patient’s previous first-line treatment regimen was R-CHOP regimen for 2 cycles; Ibrutinib combined with R-CHOP regimen for 4 cycles, and the efficacy was evaluated as disease progression (PD)
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The second-line treatment regimen is ibrutinib combined with R-ICE (rituximab combined with ifosfamide, carboplatin, and etoposide) regimen, with 2 cycles of treatment, and the efficacy evaluation is PD
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The third-line treatment plan is PD-1 combined with GEMOX (gemcitabine combined with oxaliplatin and atelizumab) for 1 cycle.
Due to the serious adverse reaction of the patient, PD-1 was discontinued, and the follow-up GEMOX treatment was followed for 1 cycle.
Evaluation of efficacy Stable disease (SD)
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The fourth-line treatment plan is R2 (rituximab combined with lenalidomide), and the treatment plan adjusted after 2 cycles of treatment is rituximab combined with carmustine, etoposide, cytarabine and melphalan.
He was discharged from the hospital one month later
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The disease relapsed one month after discharge, and autologous hematopoietic stem cell transplantation (ASCT) was performed, and PD was treated one month later
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Usually, patients with refractory or relapsed disease within 12 months after treatment have a poor prognosis, with a median OS of only 5-6 months
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After Professor Chen Xi's case sharing, the Chinese and foreign parties discussed relevant issues involved in the case
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Regarding the appropriate time to use CAR-T therapy for patients refractory to chemotherapy, Professor Robin said that CAR-T therapy is currently used as a third-line treatment for patients with refractory or relapsed LBCL
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After the patient is refractory to second-line treatment or relapses, CAR-T therapy is one of the best options among the various existing treatment options.
The earlier CAR-T therapy is started, the greater the benefit for patients
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Conclusion At the end, Professor Yang Haiyan made a summary of the meeting, thanking the experts participating in the meeting for their meticulous preparation, and hoped that CAR-T treatment could bring more hope to Chinese patients
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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