Acute promyelocytic leukemia (APL) is a highly aggressive hematological disease, and its treatment has long been a challenge in the field. Chinese scholars have contributed significantly to global APL treatment with the introduction of the arsenic trioxide (ATO) regimen. Since the publication of the APL0406 study in NEJM in 2013, the combination of all-trans retinoic acid (ATRA) and ATO has replaced ATRA combined with chemotherapy as the standard treatment for low- and intermediate-risk APL patients. However, whether this regimen is suitable for high-risk APL patients remains undetermined due to a lack of randomized controlled trials. At the 29th Annual Meeting of the European Hematology Association (EHA 2024) held from June 13-16, 2024, Dr. Uwe Platzbecker from the Leipzig University in Germany presented key findings from the APOLLO study. This study demonstrated that the combination of ATO and ATRA offers a new treatment strategy for high-risk APL patients, providing valuable insights into the current state of APL treatment and guiding future research directions and clinical practices. Oncology Frontier - Hematology Frontier invited Professor Platzbecker to share the important discoveries and clinical significance of the APOLLO study.Oncology Frontier – Hematology Frontier: Acute promyelocytic leukemia (APL) is a high-risk hematologic disease, and its treatment strategies are crucial for improving patient survival and quality of life. At this EHA conference, you presented the preliminary results of the APOLLO trial. Could you first introduce the background of this study and why ATO combined with ATRA was chosen as the new treatment strategy?
Dr. Uwe Platzbecker: The APOLLO trial aims to optimize the treatment model for APL patients. APL is a rare hematological disease, and based on clinical research from China and the United States a decade ago, a phase III clinical trial for non-high-risk APL patients was successfully published. Since then, arsenic trioxide (ATO) has shown significant efficacy in APL treatment, and its combination with all-trans retinoic acid (ATRA) has become the standard regimen. The APOLLO trial, as a follow-up to previous studies, aimed to randomly assign high-risk APL patients to either an ATRA combined with chemotherapy group (ATRA-CHT: standard AIDA induction followed by chemotherapy consolidation) or a combined ATO group (ATRA-ATO: idarubicin + ATRA + ATO induction followed by ATO consolidation), to establish a new treatment standard. This study successfully achieved its primary endpoint, establishing the combination of ATO and ATRA with a small amount of idarubicin (for induction therapy) as the new standard of care for high-risk APL patients. Here, we must express our deep gratitude to the Chinese researchers, as ATO originated from traditional Chinese medicine with over 2000 years of history. Hematology experts from Shanghai first reported the use of ATO in APL treatment, laying the foundation for the success of the APOLLO trial.
Oncology Frontier – Hematology Frontier: The AIDA regimen has long been the standard treatment for APL. In the APOLLO trial, how does the combination of ATO and ATRA compare to the standard ATRA-CHT (AIDA induction) regimen? What are the advantages or differences, and what implications do these results have for the future treatment of APL?
Dr. Uwe Platzbecker: The standard AIDA induction regimen, involving all-trans retinoic acid (ATRA) and idarubicin, has limitations due to high extramedullary toxicity, including hair loss, infection from neutropenia, bleeding events, and secondary myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) in many patients. In contrast, the APOLLO trial showed significant advantages of the ATO combined with ATRA regimen. ATO stands out due to its high anti-leukemic efficacy and lower toxicity rates, with primary side effects being mild QT interval prolongation and minor hepatotoxicity. This low-toxicity regimen offers a safer and effective treatment option for high-risk APL patients.
These findings not only provide a new perspective for current treatment strategies but also guide the future development of APL treatment, aiming to minimize patient toxicity while ensuring efficacy. With further research into the mechanisms of ATO and ATRA combination therapy, we anticipate more personalized and optimized treatment plans for APL patients.
Oncology Frontier – Hematology Frontier: The results of clinical trials are crucial for guiding clinical practice. How do you view the clinical significance of the APOLLO trial results? Can these results be immediately applied to APL patient treatment? What issues need attention in practice?
Dr. Uwe Platzbecker: Although the APOLLO trial has only released preliminary results, we can confidently say that the study has successfully achieved its primary endpoint, showing significant advantages of ATO treatment in event-free survival. Based on this, I believe that this new therapy is likely to become the standard treatment for high-risk APL patients in most clinics in the EU and my practice. With the data provided by the APOLLO trial, we are ready to apply this new therapy to our patients.
Oncology Frontier – Hematology Frontier: APL is a complex hematological disease, and treatment plans need to be tailored to individual patient conditions. How do you see the role of personalized treatment in APL treatment in the future?
Dr. Uwe Platzbecker: Distinguishing between low-risk and high-risk APL patients is crucial. Most low-risk APL patients can achieve cure, and current treatments can be effective without relying on chemotherapy. Personalized treatment may mean simplified strategies for some patients, such as omitting the entire consolidation therapy phase. For high-risk APL patients, the APOLLO trial has demonstrated that the ATO combined with ATRA regimen is equally effective, offering hope for cure to most patients. However, our main challenge is early mortality. In the first 30 days of treatment, patients may die from bleeding or thrombotic complications or may have already succumbed before treatment begins. Therefore, the key to personalized treatment is identifying those at risk of early death and ensuring they receive the ATO combined with ATRA regimen to improve survival rates.
