Oral arsenic and retinoic acid for high-risk acute promyelocytic leukemia

Abstract

Acute promyelocytic leukemia (APL) has become curable over 95% patients under a complete chemo-free treatment with all-trans retinoic acid (ATRA) and arsenic trioxide in low-risk patients. Minimizing chemotherapy has proven feasible in high-risk patients. We evaluated oral arsenic and ATRA without chemotherapy as an outpatient consolidation therapy and no maintenance for high-risk APL. We conducted a multicenter, single-arm, phase 2 study with consolidation phases. The consolidation therapy included Realgar-Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m² daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary end point was the disease-free survival (DFS). Secondary end points included measurable resident disease, overall survival (OS), and safety. A total of 54 participants were enrolled at seven centers from May 2019. The median age was 40 years. At the median follow-up of 13.8 months (through April 2022), estimated 2-year DFS and OS were 94% and 100% in an intention-to-treat analysis. All the patients achieved complete molecular remission at the end of consolidation phase. Two patients relapsed after consolidation with a cumulative incidence of relapse of 6.2%. The majority of adverse events were grade 1-2, and only three grade 3 adverse events were observed. Oral arsenic plus ATRA without chemotherapy was active as a first-line consolidation therapy for high-risk APL.Trial registration: chictr.org.cn number, ChiCTR1900023309.

Keywords: Consolidation therapy; High-risk APL; Oral arsenic; Phase 2 clinical trial; Realgar–Indigo naturalis formula.

Fig. 1

Survival among patients in ITT analysis and PP analysis. A DFS in ITT analysis; B DFS in PP analysis; C OS in ITT analysis; D OS in PP analysis; E Cumulative incidence of CMR from the beginning of the consolidation therapy in ITT analysis; and F Cumulative incidence of CMR in PP analysis. The ITT population comprised patients who enrolled and received at least one dose of study medication. The PP population comprised patients of a subgroup of ITT population who had completed the trial and underwent an end-of-therapy evaluation. Abbreviations: ITT: intention-to-treat; PP: per-protocol; DFS: disease-free survival; OS: overall survival; and CMR: complete molecular remission