Acute promyelocytic leukemia (APL) is a highly aggressive blood disorder, and its treatment has always been a challenge in the field of hematology. Chinese scholars have contributed the arsenic trioxide (ATO) regimen for global APL patients. Since the APL0406 study reported in the New England Journal of Medicine in 2013, all-trans retinoic acid (ATRA) combined with ATO has replaced ATRA combined with chemotherapy as the standard treatment for patients with intermediate and low-risk APL. However, whether this regimen is suitable for high-risk APL patients is still lacking in randomized controlled trial reports. At the 29th Annual Congress of the European Hematology Association (EHA 2024) held from June 13 to 16, 2024, Professor Uwe Platzbecker from Leipzig University in Germany presented the key results of the APOLLO study in an oral report. The study showed that the combination of ATO and ATRA provides a new treatment strategy for high-risk APL patients, offering valuable insights into the current state of APL treatment and guiding future research directions and clinical practices. "Oncology Frontier-Hematology Frontier" specially invited Professor Platzbecker on-site to share the important findings and clinical significance of the APOLLO study.

Oncology Frontier-Hematology Frontier:My first question is, APL is a high-risk hematological disease and the treatment strategies are crucial for improving patient survival and quality of life. At this EHA conference, you presented the first results of the APOLLO trial. Firstly, could you introduce the background of this research and why ATO combined with ATRA was chosen as a new treatment strategy?

Dr. Uwe Platzbecker:The APOLLO trial aimed to change the treatment paradigm in patients with acute promyelocytic leukemia, so-called APL. It’s a very rare disease, and given the inventions and also the clinical studies performed in China and the US 10 years ago, a phase 3 trial was published in so-called non-high-risk APL patients. Since then, arsenic trioxide, which is very effective in APL, plus ATRA has become the standard of care. So, APOLLO was a subsequent initiative where we tried to randomize high-risk APL patients into ATRA plus chemotherapy versus ATRA plus arsenic trioxide as the new standard of care. The study met its primary endpoint, so arsenic trioxide and ATRA plus a little bit of idarubicin（induction） is now the new standard of care for patients with high-risk APL. I have to say thanks to Chinese researchers because arsenic trioxide comes from traditional Chinese medicine and has been used there for more than 2000 years. It was actually hematologists from Shanghai who first published the use of arsenic trioxide in APL patients. So, it’s built on their research.

Oncology Frontier-Hematology Frontier:My second question is, the AIDA regimen has always been the standard treatment for APL. What advantages or differences do ATO combined with ATRA demonstrate compared to the standard ATRA-CHT（AIDA induction）protocol in the APOLLO trial? What are the implications of these results for the future treatment of APL?

Dr. Uwe Platzbecker:AIDA is an acronym and stands for ATRA plus idarubicin.  The shortcomings of this therapy, as with normal chemotherapy, are a high rate of extramedullary toxicity, such as hair loss, neutropenic infections, bleeding events, and secondary myeloid neoplasms like MDS and AML, reported in a large subset of patients. The advantage of arsenic trioxide is that it has high antileukemic efficacy but a very low toxicity rate, apart from some mild QTc prolongation and mild liver toxicity.

Oncology Frontier-Hematology Frontier:My third question is, the results of clinical trials are of great significance in guiding clinical practice. How do you view the clinical significance of the results of the APOLLO trial? Can these results be immediately applied to the treatment of APL patients? What other issues should be noted in practice?

Dr. Uwe Platzbecker: I think that although these are the first results of the APOLLO trial, we can already say that the primary endpoint was met in this study, so better event-free survival for the arsenic trioxide therapy. Therefore,  at least in my clinic and in the majority of clinics in the European Union, I think the new therapy will be the new standard treatment for all high-risk APL patients. Based on the evidence of the APOLLO trial, we can use it for our patients already.

Oncology Frontier-Hematology Frontier:As a complex blood disease, the treatment plan for APL needs to be personalized and adjusted according to the specific situation of the patient. What role do you think personalized therapy will play in APL treatment in the future?

Dr. Uwe Platzbecker: I think we have to differentiate between low-risk and high-risk APL. In low-risk APL, the majority of patients can be cured, and it’s a disease that can now be effectively treated without any chemotherapy. Personalized therapy may mean that some patients may not undergo the entire consolidation, so a de-escalation strategy could be considered. In high-risk APL, the APOLLO trial showed that arsenic trioxide plus ATRA is also very effective and can cure the majority of patients. Our challenge still is the early death rate. We see that patients die in the first 30 days of therapy because of bleeding or thrombosis, or they cannot be treated because they died before. Personalized therapy would mean identifying those patients at risk for early death and giving them a chance to undergo curative therapy with arsenic trioxide and ATRA.