Let the world hear the voice of Chinese scholars: Professor Zhang Yonghong led the team to break through innovation and promote the continuous development of the field of refractory relapsed lymphoma in children

On October 20-23, 2022, the 7th International Symposium on Childhood, Adolescent and Young Adult (CAYA) Non-Hodgkin Lymphoma was held in New York, USA.
Recent scientific and clinical advances
in biopathology, genomics, stem cell transplantation, and immunobiology in the NHL in adolescents and young adults.
At that time, top experts and scholars such as hematological oncologists, pediatric medical scientists, and basic medical scientists from all over the world will gather together to conduct in-depth discussions and analysis on hot topics in the field of children's NHL, promote the development of children, adolescents and young people in the NHL, and bring vitality and hope
to patients.

Invitations from the international community let the world hear the voices of Chinese scholars

The President of the Conference, Professor Mitchell S.
Cairo, invited Professor Zhang Yonghong of Beijing Kobo Boren Hospital, Beijing Research Center of Gaobo Medical Center (Hematology), to participate in a seminar on the theme of International Collaboration in CAYA NHL outside North America and Western Europe, and to present a pre-conference seminar entitled International Collaboration: The Chinese Children's Lymphoma Consortium keynote speech, and served as the academic host of the conference in the academic session, conveying the style
of Chinese researchers to the world.
Professor Zhang Yonghong is the only member of the organizing committee of
this conference in China.

The research of Professor Zhang Yonghong's team won the best oral presentation

At the same time, among the 29 oral reports submitted, 3 best papers were produced, and Director Liu Ying of Professor Zhang Yonghong's team won the best oral report, which was widely concerned and unanimously recognized
by the organizing committee.
The representative team reported the treatment results
in the field of refractory Burkitt lymphoma (R/R-BL) treated with CAR-T.
In the field of using CAR-T to treat refractory relapsed lymphoma, Professor Zhang Yonghong's team has brought great encouragement to clinicians at home and abroad, and also promoted the development of CAR-T therapy in the field of
refractory relapsed lymphoma.
At the same time, the National Collaborative Group for Pediatric Lymphoma (CNCL) led by Professor Zhang Yonghong has three papers accepted by the conference
.

Fine stratification treatment for treatment-new patients, the efficacy is comparable to the international level

Professor Zhang Yonghong has made great contributions to the field of pediatric lymphoma, researching and treating thousands of cases of pediatric lymphoma for nearly 20 years, and has been continuously exploring
.
In terms of treatment, the concept of "fine stratified treatment" is adopted, that is, different regimens
are adopted for different pathological types and risk factors.
Stratified treatment first began from abroad, and Professor Zhang Yonghong promoted the integration of domestic lymphoma-related treatment with international advanced medical standards
.
Precise layered treatment can promote the treatment plan of childhood lymphoma to become more standardized, the cure rate of naïve patients has been significantly improved, the cure rate of each pathological subtype of lymphoma (including NHL) admitted by the team has reached more than 80%, and the cure rate of Hodgkin lymphoma has reached more than 90%, so that more and more children have achieved survival benefits
.

Professor Zhang Yonghong also felt a responsibility to benefit more children with lymphoma across the country, and the team began to prepare for the National Childhood Lymphoma Collaboration Group (China Net Childhood Lymphoma (CNCL), and with the support of leaders and experts from various branches across the country, CNCL officially launched
in 2017 。 At the conclusion of the 4th anniversary of the collaborative group's work, the amazing efficacy data made everyone excited: the number of members grew from 11 to 30, more than 1500 lymphoma patients were admitted, and the statistics of mature B-cell lymphoma showed that the overall 2-year event-free survival (EFS) rate reached more than 90%, and different subtypes increased the baseline efficacy of CNCL by 20%-30%.

Breakthrough innovation, sequential CAR-T treatment of refractory relapsed lymphoma in children

BL is a highly aggressive mature B-cell lymphoma, primary chemotherapy can cure 80%-90% of patients, but once there is progression and recurrence, the efficacy of secondary chemotherapy is extremely poor, domestic and foreign reports show that the overall efficacy is 20%-30%, while the progression in treatment is even worse, the cure rate is almost zero
.

In addition, in many previous studies, the use of dual-target CAR-T cell therapy, CD19 CAR-T cell therapy and immune checkpoint inhibitors combined therapy to improve the persistence of CAR-T cells in patients to solve tumor cell escape after CAR-T treatment, but solving the rapid progression of R/R-B large tumors and central invasion lymphoma is still a world problem
.

In 2017, Professor Zhang Yonghong's team conducted research on this world problem, and the design idea was to carry out sequential CAR-T therapy for different B cell targets expressed by R/R-BL tumor cells, grasp the sequential timing, adjust the drug delivery strategy, may prevent tumor antigen escape and maintain the persistence
of CAR-T cells.

Professor Zhang Yonghong led the team to register for the trial study and pioneered the use of CD19/CD20/CD22 CAR-T cell sequential return treatment of R/R-BL, the first 5 cases showed a strong therapeutic effect, and the CAR-T response rate of 5 children was as high as 100%.

For the first time, the team delivered an oral speech on the first day of the conference at the 15th International Conference on Malignant Lymphoma (ICML 2019), the world's largest and highest-level academic forum covering all aspects of lymphoma, and received wide attention
.
It is worth mentioning that the research results have been paid attention to and recognized by Professor Carl H.
June of the University of Pennsylvania, known as the godfather of cell therapy, and Professor Carl H.
June specifically mentioned the results
of the study of CAR-T in the treatment of Burkitt lymphoma by the pediatric lymphoma team of Beijing Gaoboren Hospital in his keynote speech.
The team then also presented the efficacy of the team's CAR-T
in the treatment of refractory/relapsed B-cell NHL in children at the 61st American Society of Hematology Annual Meeting (ASH 2019).

In 2020, the team published this research result in
the internationally renowned hematology journal Blood.
This innovative treatment mode provides new ideas for the treatment of refractory R/R-BL and broadens the thinking
of clinical treatment.

Continue to lead CAR-T treatment of relapsed and refractory childhood lymphoma

The exploration never ends, and further, the team increased the number of patients enrolled, and in addition to the increase in the number of patients enrolled, it also increased the enrollment and extended follow-up time
of patients with central nervous system invasion and giant tumors.
A total of 23 patients were enrolled in the phase I clinical trial study, which achieved a good score of 86% in the overall CR rate, which the team presented orally
at the 25th Congress of the European Society of Hematology (EHA 2020).

So what is the long-term effect of children with R/R-BL treated with sequential car-t? If the child does not have a transplant, how long will the effect last, and will it be possible to achieve long-term survival? Based on this, Professor Zhang Yonghong's team continued to explore and track, and his research results were once again published
in the journal Blood Advance in early 2022.

The study showed that of the 23 patients enrolled in phase I clinical trials, 21 patients received CR after the last CAR-T infusion, and 18 (86%) maintained CR
until 1 and a half years after the last CAR-T infusion.
As of March 2021, the longest sustained response time was 34 months, and the 18-month progression-free survival (PFS) rate of 23 patients was 78%, including 93% of routinely enrolled patients, 78% of giant tumor groups, and 60%
of central involvement.

The study suggests that sequential CAR-T therapy may have a lasting response and is safe
for children with refractory relapsed Burkitt lymphoma (R/R-BL).
In addition, sequential CAR-T therapy may benefit
children with central nervous system (CNS) involvement in R/R-BL.

Based on the present, looking to the future, and continuing to make breakthroughs

Treatment of refractory relapsed T-cell lymphoma and anaplastic large cell lymphoma in children remains challenging
.
In the future, Professor Zhang Yonghong will also challenge to a higher difficulty, the team has begun to explore, based on the international standard protocol, combined with the team's clinical experience, for children refractory relapsed T lymphoblastic lymphoma (R/R T-LBL) to establish a whole process of hierarchical combination therapy, CD7-CART treatment of refractory relapse T-LBL research is also in progress, showing good benefits in practice, so that more children have achieved high-quality deep remission, and initial results
have been achieved.

In addition, for children with refractory/relapsed anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ALCL), the team innovatively abandoned the previous practice of repeated chemotherapy and adopted the treatment strategy of ALK kinase inhibitor combination with/without vinblastine, achieving a good effect of "four or two pounds", and most of the adverse events related to treatment
were mild and controllable.
The results of the study will also be available
soon.

To improve the efficacy of refractory relapsed lymphoma in children, the path is "immunotargeted therapy guided by molecular stratification"
.
It is expected that the results of Professor Zhang Yonghong's team's exploration in difficult areas will be announced, benefiting more children and more families
.