2021 CSCO Expert Interview｜Professor Zhang Yizhuo: New progress in the treatment of lymphoma in children and adolescents

The 24th National Conference on Clinical Oncology and the 2021 CSCO Annual Conference will be held on September 25-29, 2021.
The theme of this conference is "Focus on Innovative Research, Leading the Original Future"
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At this CSCO conference, Professor Zhang Yizhuo from the Cancer Center of Sun Yat-sen University gave a report on the topic of "New Progress in Lymphoma in Children and Adolescents and Practice in Swelling"
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Yimaitong is fortunate to invite Professor Zhang Yizhuo to share the latest progress in the treatment of lymphoma in children and adolescents
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Yimaitong: What is the current status of diagnosis and treatment of lymphoma in children and adolescents? What are the difficulties? Professor Zhang Yizhuo At present, children and adolescents’ lymphoma adopt a precise and stratified standard treatment plan.
The overall survival (OS) rate of childhood Hodgkin’s lymphoma (HL) can reach more than 90%, and children’s non-Hodgkin’s lymphoma ( NHL) OS rate can reach more than 80%
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Although the overall prognosis of lymphoma in children and adolescents is good, the current main treatment is still chemotherapy and/or radiotherapy
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With the increase of OS rate, the long-term side effects of chemotherapy and radiotherapy are worthy of attention
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The Childhood Cancer Survivor Study (CCSS) shows that children and adolescents with NHL survivors have a 3-9-fold increase in the risk of secondary tumors.
Among them, women and patients with primary mediastinal large B-cell lymphoma have a higher risk, all grades and ≥3 Grade chronic health status increased significantly compared with its sibling control group
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The St.
Jude Lifetime Cohort (SJLIFE) report showed that the cumulative burden of NHL patients with grade 1-5 chronic health conditions and chronic health conditions of survivors increased significantly compared with controls based on general community populations
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A recent CCSS study showed that the cumulative incidence of at least one grade 3-5 chronic disease in children who survived long-term NHL treatment to the age of 35 was 31.
4%, including the cumulative incidence of endocrine diseases, cardiopulmonary diseases, and second tumors.
They were 13.
3%, 10.
1%, and 9.
4% respectively
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Important factors leading to the late death of children and adolescent lymphoma survivors include secondary malignant tumors, cardiomyopathy, and pneumonia.
Significant late morbidity includes neurocognitive dysfunction, poor healthy life quality, and low social achievement
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In addition, most children and adolescents with relapsed and refractory lymphoma have a poor prognosis.
For example, after treatment with intensive chemotherapy and stem cell transplantation in children with relapsed and refractory Burkitt lymphoma, the 5-year OS rate is still less than 30%
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In summary, survivors of lymphoma in children and adolescents face the risk of late death due to secondary tumors, tumor recurrence/progression, and chronic health conditions
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Therefore, future treatment and research will focus on further reducing the intensity of treatment or finding new treatment methods on the basis of maintaining good curative effects to reduce the short-term and long-term toxicity caused by treatment, so that children and adolescents with lymphoma can get better The prognosis of the patient, a better return to society
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Yimaitong: After standardized treatment of lymphoma in children and adolescents, the prognosis is very good, so what advice do you have for advancing the standardized diagnosis and treatment of lymphoma in children and adolescents nationwide? Through the joint efforts of domestic experts, Professor Zhang Yizhuo, after standard treatment of Chinese children and adolescents with lymphoma, the curative effect and OS rate have reached foreign levels
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However, due to China's vast territory, uneven regional development, and different access to medical resources, the overall cure rate and long-term survival of children and adolescents with lymphoma are not ideal.
Some children and adolescents with lymphoma cannot be diagnosed or diagnosed early.
It is a pity that the treatment is not timely and the prognosis has not reached the expected level
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Therefore, it is recommended to promote the diagnosis and treatment of lymphoma in children and adolescents in China, and carry out relevant academic exchanges and study classes
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The National Health Commission Pediatric Malignant Tumor Expert Committee and the Pediatric Tumor Committee of the Chinese Anti-Cancer Association have all issued relevant guidelines
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In 2020, the Chinese Society of Clinical Oncology (CSCO) released the first edition of the guidelines for the diagnosis and treatment of lymphoma in children and adolescents.
The guidelines include common lymphomas in children and adolescents (such as lymphoblastic lymphoma, HL, Burkitt’s lymphoma, anaplastic The pre-treatment evaluation, pathological diagnosis, staging and treatment of large cell lymphoma [ALCL], as well as the related content of the emergency treatment of common tumors of lymphoma in children and adolescents, and the clinical application of high-dose methotrexate in children and adolescents
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The CSCO guidelines for common lymphomas in children and adolescents will be updated regularly based on the latest research progress at home and abroad
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The promotion of lymphoma guidelines for children and adolescents can improve the diagnosis and treatment level of doctors in grassroots units and underdeveloped areas, and benefit more children, adolescents and families through standardized diagnosis and treatment or timely referral
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Yimaitong: Compared with adult lymphoma, lymphoma in children and adolescents has many differences in diagnosis and treatment.
Therefore, targeted research and treatment of lymphoma in children and adolescents are of great significance
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Could you please introduce the research progress that deserves attention in the treatment of lymphoma in children and adolescents in recent years? Professor Zhang Yizhuo's psychological and physical conditions of children to adolescents (0-18 years old) are quite different from those of adult patients, and the metabolism, function, pathological subtype, biological characteristics, prognosis of the body organs of children and adolescents with lymphoma Different from adults, therefore, targeted research and treatment of lymphoma in children and adolescents is of greater significance
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In recent years, there have been many research results of new drugs and new treatment methods at home and abroad
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Childhood mature B-cell lymphomas widely express CD20.
Rituximab is a monoclonal antibody that targets CD20.
It is widely used in adult mature B-cell lymphomas and has achieved good curative effects.
However, rituximab It has limited application experience in children and adolescents with mature B-cell lymphoma
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In 2020, the results of an international multi-center, randomized, phase III clinical trial led by the European Pediatric Lymphoma International Collaboration Group (EICNHL) and the United States Children’s Oncology Collaboration Group (COG) showed that the combination on the basis of standard LMB chemotherapy regimens Rituximab can significantly prolong the event-free survival (EFS) and OS of children and adolescents with high-risk mature B-cell lymphoma, and the 5-year OS rate has increased to 95%.
This result is undoubtedly encouraging
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Chimeric antigen receptor T cell (CAR-T) immunotherapy has conducted many studies in adult relapsed and refractory large B-cell lymphoma.
CAR-T therapy has excellent efficacy in this part of patients and can prolong the patient's OS
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China's first CD19 CAR-T therapy was also approved for marketing this year, bringing hope to adults with relapsed and refractory large B-cell lymphoma
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Many centers in China are also conducting research on CD19, CD20, and CD22 CAR-T in the treatment of relapsed and refractory mature B-cell lymphoma and leukemia in children
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At present, the relevant research is still in the clinical stage, and it is expected that better research results can be obtained in the future
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In addition, the therapeutic targets of mature B-cell lymphomas in children and adolescents also include CD79A/B, PI3K, mTOR, JAK, HDAC, etc.
The application of corresponding inhibitors in children and adolescents in lymphoma is currently in clinical trials and exploratory stages
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CD30 is expressed in both HL and ALCL and is an ideal therapeutic target
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The results of a European multi-center Phase I/II clinical study published in 2018 showed that the overall response rate (ORR) of the antibody-drug conjugate Vibutuximab in the treatment of children with relapsed and refractory HL and ALCL was 47% and 53 respectively.
%, while the safety is controllable, and subsequent transplantation treatment can be continued
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In view of the excellent efficacy of verbutuximab in children with relapsed and refractory ALCL, another study has explored the efficacy of verbutuximab in newly diagnosed children with ALCL
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In 2021, researchers from the Children’s Oncology and Immunity Research Center of the National Children’s Hospital in Washington, USA published a clinical trial (COG ANHL12P1) of verbutuximab combined with chemotherapy in the treatment of newly diagnosed children with ALK-positive ALCL on Blood.
The study To evaluate the efficacy and tolerability of verbutuximab combined with standard chemotherapy (ALCL99) in newly diagnosed non-localized ALK+/CD30+ALCL children, the study included 68 patients with stage II-IV.
The complete remission (CR) rates at the second and sixth cycles were 62% and 97%, respectively, and the 2-year EFS and OS rates were 79.
1% and 97.
0%, respectively.
Compared with the standard chemotherapy regimen (ALCL99), the study can be It can effectively reduce the risk of recurrence and prolong OS.
It is especially suitable for people with high risk of recurrence.
At the same time, the program is well tolerated in children
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This study provides evidence-based medical evidence for the first-line use of verbutuximab in children and adolescents with ALCL
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In addition, ALK inhibitors that target ALK have also achieved good results in ALCL
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Sun Yat-sen University Cancer Center is conducting a single-arm, open clinical study to explore the safety and effectiveness of TQ-B3101 in patients with relapsed/refractory ALCL.
The study enrolled children and adolescents older than 6 years
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The preliminary results of the current study are encouraging, and we look forward to the publication of follow-up research results to further guide the treatment of children with ALCL
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Although the overall cure rate of HL is high, a small number of patients still relapse
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Immunotherapy has shown good effects in children with relapsed and refractory HL
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The KEYNOTE-051 study and the ADVL1412 study respectively explored the efficacy of PD-1 inhibitors pembrolizumab and nivolizumab in children with relapsed and refractory HL.
The disease control rate of relapsed and refractory HL in the two studies ( DCR) are 70% and 80% respectively
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The results of a retrospective study by the Pediatric Oncology Team of Sun Yat-sen University Cancer Center showed that 6 patients with relapsed and refractory HL who were treated with PD-1 inhibitors had an ORR of 83.
3% and a DCR of 100%, and they were well tolerated ( Frontiers in immunology, June, 2021)
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At present, the Pediatric Oncology Department of Sun Yat-sen University Cancer Center is also conducting clinical research on PD-1 inhibitors in the treatment of children with relapsed and refractory lymphomas, hoping to provide evidence-based medicine for the application of PD-1 inhibitors in Chinese children with relapsed and refractory lymphomas Evidence benefits Chinese children and adolescents with lymphoma
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CD30 CAR-T therapy is also used in HL
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In 2020, the results of a phase I/II clinical study of CD30 CAR-T in the treatment of relapsed and refractory HL in adults conducted by the University of North Carolina and Baylor College of Medicine in the United States showed that the ORR of CD30 CAR-T in the treatment of relapsed and refractory HL was 72% and was tolerable Good sex
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At present, the Texas Children's Hospital of the United States is carrying out a clinical study of CD30 CAR-T in the treatment of relapsed and refractory HL in children, and we look forward to the publication of the results of this study in the future
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Yimaitong: For the diagnosis and treatment of lymphoma in children and adolescents, what new directions do you think are worth studying? Professor Zhang Yizhuo currently has a good prognosis for newly diagnosed lymphoma in children and adolescents, but a poor prognosis for relapsed and refractory mature B-cell lymphoma
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The future research direction needs to explore new treatment methods.
Under the premise of ensuring the efficacy, try to reduce the short-term and long-term toxicity of newly diagnosed children and adolescents with lymphoma.
For patients with relapse and refractory disease, new treatment methods can be tried to prolong OS
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In addition, the pathogenesis and molecular basis of lymphoma in children and adolescents are also important research directions
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The exploration of pathogenesis and molecular basis not only contributes to the accurate diagnosis of lymphoma, but also provides in-depth understanding of the biological characteristics of lymphoma in children and adolescents, and the development of drugs with different targets
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According to the characteristics of each lymphoma, rational use of existing treatment drugs or combined application with new drugs can improve the curative effect of lymphoma in children and adolescents and improve survival
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Here I call on everyone to unite and collaborate to carry out prospective multi-center clinical research to further improve the survival rate of lymphoma in children and adolescents in China, and strive to make the prognosis of patients better
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Professor Zhang Yizhuo, Chief Physician, PhD Supervisor, Director, Department of Childhood Oncology, Sun Yat-sen University Cancer Center, CSCO China Anti-Lymphoma Alliance Standing Committee Member, CSCO China Anti-Leukemia Alliance Member, China Anti-Cancer Association Hematology Transformation Research Professional Committee Deputy Chairman and Secretary-General Member of the Standing Committee of the Hematology and Tumor Professional Committee of the Chinese Anti-Cancer Association