Patients with acute promyelocytic leukemia (APL) who received a combination therapy including arsenic trioxide, all-trans retinoic acid, and ascorbic acid (AAA) in oral form with no or minimal chemotherapy showed high rates of survival and relapse-free survival at 3 years, according to new findings from a multicenter trial in Asia reported at the 2023 ASH Annual Meeting & Exposition (Abstract 157).
The study is the first to evaluate survival outcomes from an entirely oral AAA regimen in patients with both high- and standard-risk forms of APL, a form of blood cancer in which abnormal promyelocytes harboring the PML::RARA fusion oncogene accumulate in the bone marrow. If left untreated, people with APL have a high fatality rate due to bleeding complications.
The latest study findings suggest APL can be effectively treated with this synergistic oral regimen in most cases without the need to administer any of the drugs intravenously or accompany the treatment with chemotherapy, according to researchers.
“This entirely oral regimen is highly effective, safe, and can be administered in an outpatient setting for all risk categories,” said Harinder Gill, MD, Clinical Associate Professor at the University of Hong Kong and the study’s lead author. “In addition, we found we can minimize chemotherapy in patients with all risk levels—not only in lower-risk patients—as well as in both pediatric and adult patients.”
Historically, the standard of care for both newly diagnosed and relapsed APL has included intravenous administration of arsenic trioxide and chemotherapy, which requires repeated hospital admissions and causes treatment-related toxicities. However, recent studies have suggested that an oral formulation of arsenic trioxide can perform just as well, and eliminating or minimizing chemotherapy can reduce hospitalizations, associated costs, side effects, and long-term complications.
Study Details and Findings
For the study, researchers administered an entirely oral AAA regimen to 117 patients (including 5 children) with newly diagnosed APL at sites in Hong Kong, Singapore, and mainland China between 2018 and 2023. Patients with a high white blood cell count—about 30% of study participants—received a 3-day course of chemotherapy (a regimen considered to represent “minimal chemotherapy”) to reduce the complications associated with having an overabundance of white blood cells during treatment. The rest of the participants received no chemotherapy.
Participants showed deep molecular responses to treatment, with all patients achieving a complete response initially. After a median follow-up time of 32 months, the rates of 3-year overall and relapse-free survival were 99% and 97%, respectively.
Eight patients who were initially enrolled in the study died before receiving the full drug regimen, most from bleeding in the brain as a result of their APL. One patient died during the course of the study, which was determined to be unrelated to the treatment, and one patient experienced a disease relapse, which was determined to be related to a rare genetic mutation conferring resistance to arsenic trioxide, according to Dr. Gill.
No cardiotoxicity or serious adverse events were reported, and the most common adverse events were low-grade headache and elevation of liver enzymes. APL differentiation syndrome, a known complication of treatment with all-trans retinoic acid and arsenic trioxide, occurred in over half of patients, but was resolved in all cases with the standard treatment of intravenous steroids.
Taken together, researchers say the results extend and enhance previously reported evidence on the safety and efficacy of an all-oral treatment regimen for APL.
“This brings us from a practice that involves repeated hospital admissions to an outpatient-based practice that doesn’t require a lot of intensive monitoring,” said Dr. Gill. He noted that switching from intravenous infusions to an all-oral regimen could also significantly reduce the cost of treatment.
Additional studies are being planned to further assess the use of intravenous and oral formulations of arsenic trioxide as front-line treatment for APL.
Disclosure: This study was supported by the Innovation and Technology Fund, Innovation and Technology Commission, the Government of the Hong Kong SAR. For full disclosures of the study authors, visit ash.confex.com.
