Arsenic trioxide versus Realgar-Indigo naturalis formula in non-high-risk acute promyelocytic leukemia: a multicenter, randomized trial

Abstract

Realgar-Indigo naturalis formula (RIF) is an oral form of arsenic that is effective against acute promyelocytic leukemia (APL). This multicenter, randomized, controlled trial compared the efficacy of all-trans retinoic acid (ATRA) plus RIF with ATRA plus arsenic trioxide (ATO) in a simplified regimen for non-high-risk APL. Following induction therapy with ATRA and ATO, participants were randomly assigned to receive either ATRA plus ATO or ATRA plus RIF both in a 2-week on 2-week off schedule for consolidation therapy. Once achieving molecular complete remission, the regimen was administered for a total of six cycles. All of 108 eligible patients achieved hematological complete remission after induction therapy. The median follow-up time was 29 months. The primary endpoint of 2-year disease-free survival was 97% in the ATRA-RIF arm and 98% in the ATRA-ATO arm, respectively (the ATRA-RIF arm was found to be non-inferior to the ATRA-ATO arm, [P<0.01], with a percentage difference of -1% [95% confidence interval: -4.8 to 6.9]). No deaths have been observed. Most adverse events were moderate. This study confirms the non-inferiority of RIF to ATO for non-high-risk APL, while also offering a more favorable regimen schedule for post-remission therapy (clinicaltrials gov. identifier: NCT02899169).

Figure 1.

Treatment regimen. *Indicates 1 or several repeated cycles of treatment until achieving molecular complete remission (MCR) (1-3 cycles in this trial). ATO: arsenic trioxide; ATRA: all-trans retinoic acid; RIF: Realgar-Indigo naturalis formula; HCR: hematological complete remission; MCR: molecular complete response.

Figure 2.

CONSORT diagram. ATO: arsenic trioxide; ATRA: all-trans retinoic acid; RIF: Realgar-Indigo naturalis formula; ITT: intention-to-treat.

Figure 3.

Disease-free survival in intention-to-treat analysis.