With ardent vigor and unwavering dedication, the past year has seen significant advances in the field of hematologic oncology, driven by the rapid development of innovative therapies and cutting-edge technologies. The application of novel molecular biology techniques has not only refined the prognostic stratification of Acute Myeloid Leukemia (AML) but has also fostered more precise diagnostics and treatments. At the turn of the year, Oncology Frontier – Hematology Frontier has invited Professor Hui Wei, Director of the Leukemia Diagnosis and Treatment Center at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, to review the latest advancements in the precise diagnosis and treatment of AML in 2023, and to look forward to the future prospects and directions of AML treatment.
Oncology Frontier – Hematology Frontier：In recent years, with the continuous improvement of detection technologies such as cytogenetics, molecular biology, and the status of Minimal Residual Disease (MRD), what are the latest advancements in the precise stratification of AML patients? How have these changes impacted the clinical diagnosis and treatment of AML?
Professor Hui Wei: Regarding the precise diagnosis and risk stratification of AML, the World Health Organization (WHO) updated its classification standards for hematopoietic and lymphoid tissue tumors in 2022, and the same year saw the introduction of the International Consensus Classification for Myeloid and Acute Leukemia (ICC-2022). Both classifications emphasize the role and significance of genetics in the diagnosis of acute leukemias, including AML, while further diminishing the emphasis on morphology. Particularly, the WHO classification does not emphasize the proportion of blast cells for certain genetic types anymore. Although the ICC still considers the proportion of blast cells, it strongly emphasizes the role of genetics in the diagnosis of acute leukemia. Thus, conceptually, both important international guidelines or consensus highlight the role of genetics or the nature of the disease in diagnostic typing.
In terms of specific updates in the precise diagnosis and stratification of AML, I believe there are two important points: first, internationally, the FLT3 internal tandem duplication (FLT3-ITD) has been reclassified from a high-risk group to an intermediate-risk group, thanks to the emergence of FLT3 inhibitors and MRD detection technologies that enable more precise and effective diagnosis and treatment. Secondly, with a deeper understanding of genetic mutations, mutations associated with Myelodysplastic Syndromes (MDS), including RUNX1, ASXL1, and U2AF1, are recognized as having a poor prognosis. Therefore, in the new diagnostic classification system, these mutations are classified as having a poor prognosis, which can guide doctors to more effective treatments.
Oncology Frontier – Hematology Frontier：As patient stratification becomes more precise clinically, AML treatment has also progressively moved towards precision medicine in recent years. A series of new drugs, including targeted drugs, antibody-drug conjugates, and immune checkpoint inhibitors, have emerged. Could you review some of the most promising new drug research for us? What are their potential impacts on improving the efficacy and survival benefits for AML patients?
Professor Hui Wei: In the field of AML, there are currently many targeted drugs that have been approved for marketing, including BCL-2 inhibitors, FLT3 inhibitors, and IDH inhibitors. However, in the past two years, especially in 2023, more exploration has been undertaken into new directions or indications for these drugs. For example, venetoclax was previously used in elderly patients who were not suitable for chemotherapy, but is now being tried as a first-line treatment in adult patients; FLT3 inhibitors are not only effective in treating relapsed/refractory patients, but have also shown very good efficacy in first-line treatment; IDH inhibitors are also being tested in first-line treatment in hopes of benefiting more patients. In addition, there are some unmarketed drugs, among which the most promising are menin inhibitors. They are mainly targeted at NPM1 mutations, especially in patients with MLL abnormalities. These patients have previously lacked effective targeted drugs, but menin inhibitors have shown very good efficacy in early-stage preclinical trials and Phase I clinical trials, as well as relatively good safety. Therefore, in the future, patients with MLL abnormalities and NPM1 mutations are very likely to benefit from them, thereby improving the treatment efficacy for this group of patients.
Oncology Frontier – Hematology Frontier：As clinical research on medications continues to progress, could you discuss how future AML clinical treatment strategies will change? Will traditional chemotherapy induction regimens be replaced? And how can more individualized precision treatments for AML be achieved?
Professor Hui Wei: As the foundation of myeloid leukemia treatment, I believe that chemotherapy will not be replaced in the short term. Therefore, for patients who are suitable for chemotherapy, we should continue to use it, or at least as part of the treatment. With the addition of new targeted drugs and immunotherapies, the efficacy for adult AML patients will significantly improve in the future, and elderly AML patients will receive more and more attention. Previously, relying solely on chemotherapy, elderly AML patients had poor treatment efficacy and significant side effects. The emergence of new targeted drugs and immunotherapies offers hope for elderly AML patients, especially venetoclax, which benefits many elderly patients unsuitable for chemotherapy. In the future, with more effective targeted drugs, including FLT3 inhibitors, IDH inhibitors, menin inhibitors, as well as immunotherapies and combination therapies, elderly AML might transform from a previously incurable predicament to a prospect where some patients can be cured and others can significantly extend their survival. Currently, our center is also working in this area, hoping to improve the treatment efficacy for elderly AML patients through more trials and explorations.
Oncology Frontier – Hematology Frontier：Lastly, could you summarize the unmet clinical needs in the AML field and the research directions worth further exploration in the future?
Professor Hui Wei: There are still many unmet clinical needs in the AML field. In terms of treatment methods, although small molecule targeted drugs have developed quite well, immunotherapy still has a large development space in the AML field, including antibody drugs, CAR-T drugs, all lacking effective treatment plans or strategies. Therefore, more exploration is needed in the field of immunotherapy by clinicians and researchers. From the disease aspect, one is the elderly AML patients mentioned above, who currently lack effective treatment drugs or combination schemes. Many elderly AML patients face the challenge of poor treatment efficacy. In the future, it may be necessary to apply more targeted drugs and immunotherapies to elderly AML patients to improve their survival, and even cure some patients. Another is the relapsed/refractory AML patients, whether adult or elderly AML, some patients will experience relapse and refractoriness. Therefore, in the future, it may be necessary to pay more attention to these patients, applying more and newer drugs to relapsed/refractory patients, ultimately improving and enhancing the efficacy and survival of these patients.
Professor Hui Wei
Chief Physician at the Institute of Hematology, Blood Diseases Hospital, Chinese Academy of Medical Sciences (Chinese Academy of Medical Sciences Institute of Hematology)
Director of Leukemia Diagnosis and Treatment Center
Deputy Director of the National Clinical Medical Research Center of Hematologic Diseases
Member of the Hematology Branch of Chinese Medical Association
Deputy Head of the Leukemia Lymphoma Group
Deputy Director of the Hematologic Oncology Professional Committee, Chinese Anti-Cancer Association.
Deputy Editor-in-Chief of Hematological Oncology
primarily engaged in basic and clinical research on leukemia
