Image courtesy of the Armed
Forces Institute of Pathology
The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).
The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 103/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.
Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.
“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.
“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”
Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.
Phase 3 study results
The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.
Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.
A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).
After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).
At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).
After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.
In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.
