Professor Wang Yu: Current status of transplantation and application of new drugs in ALL patients

Sponsored by the Chinese Medical Association, Hematology Branch of Chinese Medical Association, Leukemia and Lymphoma Group of Hematology Branch of Chinese Medical Association, Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences), First Affiliated Hospital of University of Science and Technology of China The 16th National Leukemia and Lymphoma Academic Conference hosted by the Chinese Medical Association will be held in Hefei, Anhui Province on October 8-10, 2021
.

At this conference, Yimaitong was fortunate to invite Professor Wang Yu from Peking University People's Hospital to share the status of transplantation of patients with acute lymphoblastic leukemia (ALL) and the application of new drugs
.

Yimaitong: First of all, could you please introduce the current status of ALL patients receiving transplantation, and what is the overall prognosis of ALL patients after receiving transplantation? Statistics from Professor Wang Yu’s International Bone Marrow Transplant Registry (IBMTR) and the European Society for Blood and Bone Marrow Transplantation (EBMT) show that the number of ALL patients receiving allogeneic hematopoietic stem cell transplantation (Allo-HSCT) ranks third among all diseases, approximately 10%-20% of patients receiving Allo-HSCT are ALL patients
.

The proportion of ALL patients receiving Allo-HSCT in China is relatively higher.
Data from the domestic registry shows that last year, more than 13,000 patients in China received Allo-HSCT, of which more than 2,800 were ALL patients
.

In China, 65% of ALL patients who received Allo-HSCT received haplotype Allo-HSCT
.

The curative effect of ALL patients receiving Allo-HSCT is closely related to the remission state after induction therapy
.

The long-term survival rate of ALL patients who received Allo-HSCT in the first complete remission (CR1) state was more than 60%, but the long-term survival rate of ALL patients who received Allo-HSCT without reaching the CR state was less than 30%
.

More than 300 registration data from multi-centers across the country show that the long-term survival rate after Allo-HSCT for ALL patients who have not reached the CR status under the “full-process management including enhanced pretreatment and immunotherapy (DLI), residual monitoring, etc.
” Up to 50%
.

But for ALL patients who have not reached CR status and do not take any intensive intervention, the long-term survival rate after Allo-HSCT is less than 20%
.

Yimaitong: The emergence of many new drugs provides a better bridge for ALL patients Transplantation treatment options, can you please introduce the new drug bridging schemes that are worth paying attention to in the treatment of ALL? Professor Wang Yu currently has a good therapeutic prospect for new drugs in ALL.
Among them, the CD19/CD3 bispecific antibody Belinto Odan Anti-bacterial is a new drug worthy of attention in the field of B-cell ALL (B-ALL) treatment.
Both patients with relapsed and refractory (R/R) B-ALL or patients with minimal residual disease (MRD) positive B-ALL can pass Bellin Toolumab treatment has achieved a better remission state and effectively bridges subsequent transplantation
.
The
phase III TOWER study compared the efficacy and safety of belintolumab and standard chemotherapy in the treatment of R/R B-ALL.
The results of the study showed that Belintoux significantly prolonged the overall survival (OS) of patients with R/R B-ALL (median OS: 7.
7 months vs 4.
0 months; 6-month OS rate: 54% vs 39%; P= 0.
01)
.

For patients with R/R B-ALL receiving salvage treatment for the first time, belintolumab reduced the risk of death, prolonged OS (11.
1 months vs 5.
5 months; P=0.
016), and achieved higher The complete response (CR) rate (44% vs 29%)
.

In addition, belintoomab has good safety in the treatment of R/R B-ALL, and the incidence of ≥3 grade adverse events (AE) is lower than that of the standard chemotherapy group.
After that, 2/3 of the patients have bridged the transplantation.
The recurrence rate after transplantation is only 7% and TRM is 13%
.

Recently, belintoomab has also shown good efficacy for newly treated ALL (including PH+ALL and pediatric patients)
.

For MRD-positive patients treated with belintoomab, the effect of bridging transplantation on OS is different.
The BLAST study shows that MRD-positive patients with >=CR2 can benefit more from bridging transplantation
.

In addition to B-ALL, some new drugs in recent years have also shown good efficacy in T-cell ALL (T-ALL), which can effectively bridge Allo-HSCT
.

A study included 118 R/R T-ALL patients to explore the efficacy of DNA synthesis inhibitor Nelarabine as a rescue therapy in R/R T-ALL patients
.

The results of the study showed that the CR rate of Nelarabine treatment of T-ALL reached 36%, the overall response rate (ORR) reached 50%, the 1-year OS rate reached 37%, and 40% of R/R T-ALL patients successfully received Allo-HSCT
.

In addition to Nelarabine, the BCL-2 inhibitor Veneclax can also be used as a bridging treatment option in early precursor T cell ALL (ETP-ALL)
.

At present, a number of research reports show that the combination of Venecla (combined drugs including bortezomib, decitabine D-CAG, Nelarabine, etc.
) can bring better efficacy for ETP-ALL patients and effectively bridge the follow-up Allo- HSCT
.

It is hoped that more studies will be carried out in the future to further verify the efficacy of related new drugs in ALL, and bring better new drug bridging programs for ALL patients
.

Yimaitong: At present, some studies are exploring the feasibility of new targeted drugs and cell therapies as maintenance treatment options after transplantation.
What are your expectations for the use of these new drugs and therapies in maintenance treatment? Professor Wang Yu currently faces the main problem of ALL patients after Allo-HSCT is the recurrence of the disease, which is also one of the main reasons for the death of ALL patients after Allo-HSCT
.

Although the current new drugs and cell therapies have shown good efficacy in the treatment of ALL, whether these new drugs and new therapies can improve the MRD status after Allo-HSCT and reduce the disease recurrence rate of ALL patients needs more research.
To verify
.

At present, new drugs and new therapies for ALL are mostly used for salvage or early treatment of recurrence or MRD positive, and the progress in maintenance treatment after transplantation is lagging behind that of acute myeloid leukemia (AML)
.

However, it is hoped that related studies can obtain better results, bring more options for maintenance treatment after Allo-HSCT in ALL patients, and improve the survival outcome of ALL patients after Allo-HSCT
.

Professor Wang Yu, Ph.
D.
, Chief Physician, Associate Professor, PhD Supervisor, Director of the Bone Marrow Transplantation Department, Peking University People’s Hospital, Haidian District, Peking University People’s Hospital.
Member and Secretary of the 10th Hematopoietic Stem Cell Application Group of the Branch, the 10th Youth Committee of the Hematology Branch of the Chinese Medical Association Director, Member of the Hematology Branch and Working Secretary of the Chinese Medical Care International Exchange Promotion Association, China Anti-Cancer Association Hematological Oncology Professional Committee China MDS/ MPN Working Group Deputy Leader, Standing Committee Member of the Hematology Branch of the Chinese Geriatrics Association Member of the Hematology Professional Committee of the Chinese Society of Integrative Medicine, Standing Committee Member of the Hematology Professional Committee of the Beijing Society of Integrative Medicine improve together