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SAN DIEGO -- An all-oral regimen for newly diagnosed acute promyelocytic leukemia (APL) proved "highly effective and safe," with most patients avoiding chemotherapy altogether, a researcher reported here.

In a multicenter study conducted in Asia, all 117 patients treated on protocol with the all-oral regimen of arsenic trioxide, all-trans retinoic acid (ATRA), and ascorbic acid achieved a complete remission. About a fifth of high-risk patients also received a short-course of chemotherapy.

At 3 years, relapse-free survival and overall survival rates reached 97%, and no significant heart toxicity was observed, according to Harinder Gill, MD, of the University of Hong Kong, who detailed the results at the American Society of Hematology annual meeting.

APL is a rare and distinct subtype of acute myeloid leukemia, with diagnosed in the U.S. each year.

The disease is highly curable, but early death represents a major problem in APL -- from bleeding episodes or other disease-related complications -- and is exacerbated by delayed treatment initiation, Gill explained during a press briefing.

More than 90% of patients with APL go into remission with standard treatment, but relapse occurs in 5% to 10%, especially in those without access to arsenic trioxide, he said. Long-term survival improves from 80% to 90% when patients have access.

"ATRA is oral in the U.S., but the arsenic part of the treatment regimen is IV, and it's a real pain in the tuchus to give," said Aaron Gerds, MD, of the Taussig Cancer Institute and Cleveland Clinic Foundation in Ohio, who was not involved in the study.

During consolidation, "it's IV every day for 2 weeks at a time -- 2 weeks on, 2 weeks off," he said. "These patients are driving to the cancer center -- sometimes an hour, 2 hours away -- have to get their EKG, have to get their labs drawn because there is the cardiotoxicity."

While IV and oral doses of arsenic trioxide have similar bioavailability, peak levels can be higher shortly after IV dosing, putting patients at risk for QTc prolongation, said Gill.

Gerds, who served as press briefing moderator, said that if the all-oral regimen were to be "implemented into clinical practice, such an approach could vastly improve patient care and make care easier to deliver, especially in remote areas."

Oral arsenic trioxide is currently available in Hong Kong and for export on a "named-patient basis," said Gill, and he noted that a pivotal phase III trial is planned.

From January 2018 to September 2023, researchers identified 125 patients with APL (median age 49 years, 59% female), including five pediatric cases. About one-fourth had high-risk disease based on leucocyte count (>10 × 10⁹/L) and the rest were standard risk (≤10 × 10⁹/L). The all-oral regimen was designed for all risk groups and age groups, with the arsenic trioxide dosage adjusted by weight.

Eight of the screened patients presented in a "moribund" state and had early deaths, according to Gill (six due to intracranial hemorrhage and two from ), and received treatment off protocol.

The 117 patients without life-threatening complications at presentation were recruited to the study and received the all-oral induction regimen on protocol.

As the goal was to obviate the need for chemotherapy in most patients, arsenic trioxide and ATRA acted as the backbone, with ascorbic acid included to increase arsenic trioxide's effectiveness, said Gill. In total, 21% of the younger, high-risk patients also received a 3-day course of IV daunorubicin during induction.

After complete remission, consolidation and maintenance cycles were chemotherapy-free. At data cutoff, 63 patients had completed 2 years of maintenance therapy with the all-oral regimen. Overall survival, relapse-free survival, and safety were the study's primary endpoints.

Two deaths occurred during follow-up: one patient relapsed and died from refractory APL, and another died due to unrelated gastrointestinal bleeding while in remission.

Transaminitis (50%) and headache (36%), mostly low-grade, were the most common non-hematological toxicities.

Differentiation syndrome occurred in 58% of the participants, all within 2 weeks of treatment initiation, and all cases were resolved with dexamethasone. No cardiotoxicity or grade 3/4 hepatotoxicity was observed, and there were no toxicity-related discontinuations or treatment-related deaths.

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