Editor's Note: To further enhance the diagnostic and treatment techniques for leukemia and lymphoma in China, the 8th Hematology Oncology Academic Conference was held from July 26 to 28 in Harbin. This event was jointly organized by the Chinese Society of Clinical Oncology (CSCO), the CSCO Leukemia Expert Committee, and the Lymphoma Expert Committee, and co-hosted by the Harbin Institute of Hematology and Oncology and Peking University Cancer Hospital. The conference aimed to provide a significant platform for in-depth learning and extensive exchange among experts and scholars in the field of hematologic oncology. On this occasion, Hematology Frontier had the privilege of inviting Dr. Qian Jiang from Peking University People's Hospital to share her insights on the treatment models and unmet needs for newly diagnosed chronic myeloid leukemia (CML) patients.Hematology Frontier: Could you give us an overview of the current standard treatment model for newly diagnosed chronic myeloid leukemia (CML) patients? How has it evolved or improved compared to the past? What role does personalized treatment play in disease management?
Dr. Qian Jiang: Chronic myeloid leukemia (CML) is a chronic progressive hematologic malignancy that has seen significant advancements in treatment in recent years. Today, there are several highly effective treatment options available in clinical practice. First- and second-generation tyrosine kinase inhibitors (TKIs) are widely adopted as the standard treatment regimen for CML across various countries. However, selecting the most appropriate treatment plan for a patient is a complex decision-making process that requires consideration of multiple factors.
Firstly, clinical characteristics such as the patient’s age, comorbidities, and disease risk level are crucial in developing a treatment plan. For example, younger patients might be more suitable for drugs with long-term efficacy and lower side effects, while older patients or those with severe comorbidities might require a more gentle treatment approach. Additionally, the patient’s genotype, disease stage, and expected response to treatment are important factors to consider.
Furthermore, healthcare professionals must thoroughly understand the potential toxicities of the drugs, including hematologic and non-hematologic toxicities, as well as possible long-term complications. The patient’s financial capability is also a practical consideration, as the cost differences between drugs may influence the treatment choice.
Although patients currently have a wide range of treatment options, creating a personalized treatment plan requires clinicians to comprehensively weigh all relevant factors. It is important to note that not all treatment plans guarantee success. Even if a treatment plan is well-matched to the patient’s condition, there may still be issues such as treatment intolerance, treatment failure, or drug resistance. Therefore, close monitoring throughout the treatment process is critical, especially for patients at high risk of drug resistance and intolerance.
In summary, CML treatment requires a holistic consideration of patient-specific differences and the characteristics of the treatment drugs to formulate a personalized treatment plan. Physicians should select the most suitable treatment based on the patient’s specific condition and continuously monitor the treatment process to ensure the best possible therapeutic outcome and quality of life for the patient.
Hematology Frontier: During your presentation, you mentioned unmet clinical needs in the treatment of CML. Specifically, what do you believe are the biggest challenges currently facing CML patients? How should research and clinical practice address these challenges?
Dr. Qian Jiang: Despite the availability of multiple effective and accessible treatment options in CML therapy, several challenges persist in clinical practice. The failure of drugs to meet expected efficacy or the inability of some patients to tolerate their safety profile are two major issues currently faced. These challenges not only affect patient compliance, potentially leading to treatment discontinuation, but also represent unmet needs in the current field of clinical medicine.
Drug resistance is a significant issue in CML treatment, which may arise due to genetic mutations, differences in drug metabolism, poor drug absorption, and other factors. Approximately 20% to 30% of patients, particularly those in the chronic phase of the disease, may encounter drug resistance. To address this challenge, clinicians need to conduct comprehensive examinations, including genetic testing, to identify mutations that may lead to resistance to specific drugs. At the same time, physicians should consider the pharmacokinetics of the drugs and patient-specific factors such as age, gender, and liver and kidney function to select the most appropriate treatment plan.
Drug intolerance is another concern, where drug-related adverse reactions may prevent some patients from continuing treatment—an issue typically referred to as drug intolerance. The severity of these adverse reactions varies among individuals, and some patients may be particularly sensitive to certain drugs. To reduce the occurrence of adverse reactions, physicians should conduct a thorough assessment before treatment, including a detailed history of previous illnesses, drug allergies, and comorbidities. During treatment, physicians should closely monitor the patient’s response and adjust the drug dosage or switch treatment plans as necessary.
To address these issues, physicians can take several measures: First, thorough communication with the patient before treatment to clearly inform them of potential risks and adverse reactions and the strategies to manage them. Second, selecting the most appropriate drug and treatment plan based on the patient’s specific condition to achieve the best therapeutic effect and minimize adverse reactions. Additionally, during treatment, physicians should regularly monitor the patient’s condition and drug response, adjusting the treatment plan as necessary to address potential resistance and intolerance issues. The treatment of CML also requires a multidisciplinary team approach, including hematologists, pharmacists, and radiologists, to provide comprehensive treatment and care for the patient. Moreover, encouraging research into new drugs and treatment methods is essential to overcome the limitations of existing therapies and offer patients more treatment options.
Hematology Frontier: Looking to the future, what do you see as the future direction of CML treatment? Are there any emerging treatment methods or strategies that you believe will significantly impact the treatment and prognosis of CML patients?
Dr. Qian Jiang: In CML treatment, targeted therapies have become the standard treatment approach. These therapies significantly improve patient outcomes by specifically inhibiting disease-related molecular targets. However, these drugs often require long-term use, and patients may experience chronic and persistent adverse reactions over time. These adverse reactions include, but are not limited to, gastrointestinal reactions, edema, muscle cramps, and liver and kidney function damage. More seriously, some drugs may also cause cardiovascular or pulmonary complications, affecting the patient’s quality of life and tolerance, and may even necessitate dose adjustments or treatment discontinuation.
Given this, exploring which patients can safely discontinue or successfully reduce the dosage of these drugs without compromising disease control has become a key topic in future clinical research. Achieving this goal requires in-depth assessment and monitoring of the patient’s disease state, drug response, and individual differences. Additionally, identifying biomarkers that may predict successful drug discontinuation through precision medicine approaches is a current research hotspot.
Looking ahead, the development of CML treatment will mainly focus on two areas: First, optimizing drug discontinuation and dose reduction strategies. With a deeper understanding of the biological characteristics of the disease and more accurate assessments of individual differences, future treatment is expected to become more personalized, aiming to reduce drug exposure and lower the risk of long-term toxicity while maintaining disease control. Second, addressing drug resistance mechanisms. Although the currently available TKIs have shown high therapeutic efficacy, resistance remains a significant challenge in CML treatment. Future research should aim to uncover the molecular mechanisms of resistance and develop drugs that can overcome resistance, providing more treatment options for patients. At the same time, future treatment should focus on developing new drugs with higher safety profiles and better tolerability, offering new opportunities for patients who are intolerant to existing drugs.
In conclusion, CML treatment is moving towards greater personalization and precision. By deeply studying the biology of the disease, the mechanisms of drug action, and patient-specific differences, future treatment will place more emphasis on the quality of life and long-term health of patients. Additionally, the development of new drugs and strategies will provide strong support for overcoming current treatment challenges.
Dr. Qian Jiang
MD, Chief Physician, Secondary Professor, PhD Supervisor Deputy Director, Department of Hematology, Peking University People’s Hospital Deputy Director, Peking University People’s Hospital Qingdao Hospital Member, National Representative Committee, International CML Foundation Member, International Leukemia and Related Diseases Comparative Research Association Member, Hematology Branch of the Chinese Medical Association, Deputy Leader of the Leukemia-Lymphoma Group Chairman, Hematology Branch, Beijing Medical Association Chairman, Leukemia Professional Committee of the Chinese Anti-Cancer Association for Integrated Chinese and Western Medicine Chairman, Leukemia Branch, China Medical Education Association
