Prof. Wang Ying: Advances in the treatment of acute myeloid leukemia 2021 China Oncology Congress

Acute myeloid leukemia (AML) is a relatively common adult hematological malignancy, the incidence increases with age, and the overall prognosis of AML patients is poor
.

In the field of AML treatment, from the advent of the classic "7+3" chemotherapy regimen in 1973 to the FDA approval of Gemtuzumab ozogamicin (GO) in 2000, no new drug was born
.

But since 2017, with the development of the AML treatment field, the types of AML drugs have also experienced a blowout growth, so what is the current AML treatment landscape? At the 2021 China Conference on Oncology (CCO) held online from April 14 to 17, 2022, Professor Wang Ying from the Hospital of Hematology, Chinese Academy of Medical Sciences, with the title of "Progress in the Treatment of Acute Myeloid Leukemia", introduced the current status of AML.
Treatment pattern
.

Exploration of Traditional Chemotherapy Scheme>>>>Exploration of Induction Therapy Prof.
Wang Ying first said that although no new drugs have come out in the field of AML treatment for a long time, the optimization and exploration of the "7+3" treatment scheme by clinicians did not stop
.

A study published in the New England Journal in 2009 demonstrated for the first time that the increase of daunorubicin (DNR) from 45mg/m² to 90mg/m² significantly improved the remission rate and overall survival (OS) of AML patients aged ≥60 years
.

In the subgroup analysis of this study, patients in the low- and intermediate-risk groups could achieve a survival benefit from DNR of 90 mg/m², while there was no significant improvement in survival and remission rate in high-risk patients; AML patients with NPM1 mutations Can also significantly benefit from 90mg/m² DNR
.

Subsequent studies have also confirmed that DNR 60-90mg/m² can bring significant survival benefits to AML patients compared with 45mg/m²
.

Chinese adult acute myeloid leukemia (non-acute promyelocytic leukemia) diagnosis and treatment guideline (2021 edition), Chinese Society of Clinical Oncology (CSCO) 2021 edition guideline, NCCN guideline (2020 edition) all recommend DNR 60-90mg/m² combined with adjuvant Glycocytidine (Ara-c) 100-200mg/m² is used for the treatment of AML patients who are suitable for chemotherapy (fit)
.

A single-arm study by the team of Professor Wang Jianxiang from the Hospital of Hematology, Chinese Academy of Medical Sciences explored the efficacy of homoharringtonine (HHT) combined with the traditional "7+3" regimen (HAD regimen).
The CR rate of AML patients reached 80.
4%, and the 3-year The OS rate reached 31.
5%, and the 3-year disease-free survival (DFS) rate reached 41.
5%.
Subsequently, on the basis of the HAD regimen, the dose of cytarabine (Ara-c) was increased to a moderate dose, and the survival rate of AML patients was significantly higher than that of AML patients.
The remission rate was further improved, the CR rate reached 92.
0%, the 3-year OS rate reached 58.
7%, and the 3-year DFS rate reached 63.
4%
.

In 2020, Professor Wang Jianxiang's team published the results of a prospective randomized controlled study comparing the efficacy of medium-dose Ara-c with standard-dose Ara-c in the journal Clinical Cancer Research.
Compared with the standard-dose group, the CR rate of the medium-dose group increased to 86.
8%, and adverse events did not increase; in the subgroup analysis, patients in the intermediate-risk group, low-risk group, AML-ETO1 and CEBPA double mutation patients benefited more from the intermediate dose
.

The Chinese guidelines for the diagnosis and treatment of adult acute myeloid leukemia (non-acute promyelocytic leukemia) (2021 edition) and the 2021 edition of the Chinese Society of Clinical Oncology (CSCO) guidelines also recommend the HAD regimen as the first-line treatment for fit AML patients
.

Professor Wang Ying concluded from the above-mentioned trials that the improvement of the above induction protocol significantly improved the survival and remission of AML patients with low-risk, intermediate-risk, NPM1 mutation, AML-ETO1, and CEBPA double mutations, but the survival of high-risk AML patients failed to improve.
Benefiting from the optimization of traditional regimens, it requires the development and application of new drugs to improve prognosis
.

>>>>Exploration of Post-Remission Treatment For the treatment options after complete remission (CR), the Chinese Guidelines for the Diagnosis and Treatment of Adult Acute Myeloid Leukemia (Non-Acute Promyelocytic Leukemia) (2021 Edition) gives perfect recommendations based on prognosis.
Stratified treatment is very important.
The specific treatment content is summarized by Professor Wang Ying as shown in Figure 1
.

 Figure 1 For maintenance treatment after transplantation, the results of a study published in Lancet Oncology in 2020 by the team of Professor Liu Qiqi from Nanfang Hospital Affiliated to Southern Medical University showed that FLT3-ITD-positive AML patients were treated with sorafenib after transplantation, and the cumulative Recurrence rate (CIR) decreased and OS rate increased
.

In addition, the results of a study published in the journal of clinical oncology in 2020 by the team of Professor Zhang Xi from Xinqiao Hospital of Army Medical University showed that decitabine maintenance treatment after transplantation in AML patients without special mutations reduced CIR and improved OS rate
.

These findings are also included in the recommendations of the Chinese adult acute myeloid leukemia (non-acute promyelocytic leukemia) diagnosis and treatment guidelines (2021 edition)
.

The treatment of new drugs is explored.
Elderly (≥60 years old) and unfit for chemotherapy (unfit) AML patients have poor prognosis and lack of effective treatment when only the "7+3" regimen is available.
However, with the advent of new drugs, such as BCL2 inhibitors Veneclax, the demethylating drugs decitabine and azacitidine, are increasingly available for elderly and unfit AML patients
.

Professor Wang Ying summarized the treatment process of elderly (≥60 years old) and unfit AML patients, as shown in Figure 2
.

 Figure 2 How is the treatment progress of new drugs in AML patients suitable for chemotherapy? Professor Wang Ying introduced in detail that in 2020, the New England Journal published a study on the efficacy of veneclax combined with azacitidine compared with single-agent azacitidine in fit AML patients with intermediate and high-risk cytogenetic characteristics.
The results showed that Veneclax combined with azacitidine can significantly improve the CR+CRi rate and OS rate of patients in different subgroups
.

In 2021, the journal of clinical oncology published a study of veneclava combined with FLAG-IDA in patients with relapsed and refractory AML (R/R AML) and treatment-naïve AML.
The overall response rate (ORR) of AML patients reached 97%, and the MRD-negative CR rate reached 96%, which made the ORR of R/R AML patients reach 72%, and the MRD-negative CR rate reached 69%.
There is also a significant benefit in survival.
The adverse event is bone marrow suppression.
main
.

In addition to the aforementioned veneclax studies, the FLT3 inhibitor geritinib has also made significant progress.
In 2019, the New England Journal published a study of geritinib and salvage chemotherapy for R/R AML patients with FLT3 mutations.
The efficacy comparison study showed that compared with the salvage chemotherapy group, the gilritinib group could significantly improve the ORR rate (67.
6% vs 25.
8%), and more patients could be bridged to allogeneic hematopoietic stem cell transplantation, and the median OS Significant improvement (9.
3 months vs 5.
6 months)
.

Professor Wang Ying concluded in this part that the expansion of new drugs not only brings new treatment hope for elderly, unfit, relapsed and refractory AML patients, but also improves the survival rate and survival rate of fit AML patients with intermediate and high-risk genetic characteristics.
remission rate
.

In addition, Professor Wang Ying also emphasized that chromosomal and second-generation gene mutation testing should be performed for R/R AML patients to identify the presence or emerging of specific abnormal chromosomes and mutated genes, and then provide help for treatment selection
.

Summary Professor Wang Ying finally concluded that with the improvement of transplantation technology and the optimization of traditional chemotherapy regimens, the survival rate and remission rate of AML patients have increased year by year; like other hematological malignancies, AML also relies on accurate diagnosis and stratified treatment.
Moreover, with the advent of various targeted drugs, accurate diagnosis and prognostic stratification are becoming more and more important for the treatment of AML, and clinicians need to pay attention accordingly
.

Prof.
Wang Ying, Director, Assistant Chief Physician, MD, Director, Leukemia Center, Hematology Hospital, Institute of Hematology, Chinese Academy of Medical Sciences, MD, Member of the Standing Committee of the 6th Hematology and Oncology Committee of China Anti-Cancer Association, 1st Youth Working Group of the Hematology Rehabilitation Committee of China Association of Rehabilitation Medicine Vice-chairman Member of the Standing Committee of the Leukemia Branch of the Chinese Medical Education Association Member of the Professional Committee of Hematopoietic Stem Cell Transplantation and Cell Therapy of the Chinese Medical Education Association Member of the Experimental Diagnostics Group of the 11th Committee of the Hematology Branch of the Chinese Medical Association ·The editorial board member of the journal Lymphoma is a postdoctoral fellow at the Winship Cancer Institute of Emory University, mainly engaged in clinical and basic research work on leukemia.