Oral regimen provides curative, chemotherapy-free treatment of acute promyelocytic leukemia
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Key takeaways:
- All patients who received the oral regimen achieved an initial complete remission.
- Survival rates remain more than 99% after 3 years of follow-up data.
SAN DIEGO — Oral arsenic trioxide proved safe and effective when used as part of a regimen for treatment of acute promyelocytic leukemia, study results presented at ASH Annual Meeting and Exhibition showed.
The oral formulation of arsenic trioxide demonstrated bioavailability equivalent to that of IV products, according to study investigators.
“All patients who received this regimen experienced complete remission, and they did so within four weeks of starting treatment,” Harinder Gill, MBBS, MD, FRCP, FRCPath, a specialist in hematology and hematological oncology and clinical associate professor in the department of Medicine at The University of Hong Kong’s School of Clinical Medicine, said during a press briefing.
Background
Acute promyelocytic leukemia (APL) is a fast-progressing disease with a high cure rate using currently available treatment regimens, according to Gill.
The standard care for relapsed or newly diagnosed APL — also known as the AAA regimen — includes IV arsenic trioxide plus all-trans retinoic acid and ascorbic acid. It is often combined with chemotherapy, especially in high-risk patients.
Despite a better than 90% cure rate, Gill said that unequal access to the IV form of arsenic trioxide results lower long-term survival rates in real-world treatment settings compared with clinical trials, especially in “resource-constrained countries.”
“[Our] rationale was to design a regimen with minimal chemotherapy that is entirely oral ... to reduce short-term and long-term complications, reduce the need for hospitalizations and improve quality-of-life,” he told Healio.
“Furthermore, oral arsenic trioxide is available at much more affordable compared [with] intravenous arsenic trioxide,” Gill added. “This is particularly important in Asia and many places around world where intravenous arsenic trioxide is only available at a high cost.”
Methodology
Harry and colleagues conducted a prospective multicenter study to evaluate the safety and efficacy of an oral AAA induction regimen for five pediatric patients (median age, 12 years; range, 3-15) and 116 adults (median age, 49 years; range, 19-91) with newly diagnosed APL.
The analysis also included evaluation of molecular responses to the oral AAA regimen during induction, consolidation and maintenance therapy.
The investigators divided study participants into standard- ( 10 × 109/L) and high-risk (> 10 × 109/L) groups based on leucocyte count.
Standard- and high-risk patients aged 65 years or greater received AAA regimen as induction therapy, whereas high-risk patients over the age of 65 years received AAA induction plus daunorubicin.
Study participantsssss who achieved complete remission then received AAA consolidation and maintenance therapy.
The study’s primary outcome measurements included OS, relapse-free survival and safety, with molecular response serving as a secondary outcome.
Key findings
The final analysis included 117 patients who received an oral AAA induction regimen between January 1, 2018, to July 22, 2023, as seven adults considered high-risk died before receiving treatment. All patients treated in the study achieved an initial complete remission after oral AAA induction therapy.
At a median follow-up of 29 months, 56 patients (49%) received 2 years of oral AAA maintenance therapy, with only one patient experiencing disease relapse 12 months after completing the oral AAA maintenance regimen. Another patient died from gastrointestinal bleeding unrelated to treatment or their diseases.
Researchers reported a 3-year OS rate of 99.1% and 3-year relapse-free survival rate of 97.9%.
Safety results showed no cardiotoxicity associated with the oral AAA regimen. Additionally, no study participants discontinued treatment due to adverse events.
The most frequent treatment-related nonhematologic adverse events included transaminitis (47.3%) and headache (28%).
APL differentiation syndrome occurred in 67 patients after the start of oral AAA therapy. All cases resolved after treatment with IV dexamethasone.
Clinical implications
The results suggest that oral arsenic trioxide can replace IV formulations without affecting treatment outcomes, according to Gill.
“An oral arsenic trioxide-based regimen is safe and highly effective in APL, irrespective of age and risk categories,” he told Healio. “A pivotal phase 3 study of oral AAA vs. intravenous [arsenic trioxide plus all-trans retinoic acid] is being planned.”
Collapse
Gill H, et al. Abstract 157. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2023; San Diego.
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