ATRA Plus Arsenic Trioxide Could Be New Standard for Some APL Patients

The final results of the APL0406 trial indicated that the combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) for the treatment of low- or intermediate-risk acute promyelocytic leukemia (APL) had advantages compared with ATRA plus chemotherapy (CHT). Data from an initial 156 patients in the APL0406 trial showed that ATRA-ATO was at least not inferior to ATRA-CHT; however, these final results show that use of ATRA-ATO resulted in a significantly greater and sustained antileukemic efficacy compared with ATRA-CHT.

“Compared with our previous report in which no significant differences in disease-free survival and cumulative incidence of relapse rates were found, we report here that the CHT-free approach based on ATRA-ATO resulted in higher antileukemic efficacy,” wrote Uwe Platzbecker, MD, of Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, and colleagues, in the Journal of Clinical Oncology. “In addition, the present analysis conducted in a substantially extended cohort of patients with prolonged follow-up revealed significantly improved differences in all other analyzed outcomes (event-free survival, overall survival, and disease-free survival) compared with the initial report.”

The APL0406 trial was a phase III noninferiority trial that randomly assigned 263 patients aged 18 to 71 with newly diagnosed, low- or intermediate-risk APL to receive ATRA-ATO or ATRA-CHT from 2007 to 2013.

A similar percentage of patients assigned to ATRA-ATO and ATRA-CHT achieved complete remission (100% and 97%; P = .12). With a median follow-up of 40.6 months, patients assigned to ATRA-ATO had significant improvements in event-free survival (97.3% vs 80%; P < .001), cumulative incidence of relapse (1.9% vs 13.9%; P = .0013), and overall survival at 50 months (99.2% vs 92.6%; P = .0073).

During follow-up, two relapses occurred in patients assigned ATRA-ATO at 22 and 27 months, and 15 occurred in patients assigned ATRA-CHT at a median of 14 months. In addition, two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm.

A quality-of-life analysis showed that severity of fatigue was significantly lower in patients treated with ATRA-ATO compared with ATRA-CHT after induction therapy (P = .008).

“These data indicate that the advantage of ATRA-ATO over ATRA-CHT increases over time and that the inclusion of ATO in the treatment of low- or intermediate-risk APL not only reduces mortality and hematologic toxicity, but also results in improved and sustained antileukemic activity,” the researchers wrote. “Neither additional fatal events nor further relapses were recorded in patients randomly assigned to ATRA-ATO in this extended cohort.”

Based on these results, ATRA-ATO should be a new standard of care for low- and intermediate-risk patients with APL, the researchers concluded.