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

J Hematol Oncol. 2022 Oct 18;15(1):148. doi: 10.1186/s13045-022-01368-3.

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.

Publication types

  • Multicenter Study
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Arsenic Trioxide / adverse effects
  • Arsenic Trioxide / therapeutic use
  • Arsenic* / therapeutic use
  • Arsenicals* / adverse effects
  • Humans
  • Leukemia, Promyelocytic, Acute* / drug therapy
  • Oxides / therapeutic use
  • Treatment Outcome
  • Tretinoin / therapeutic use

Substances

  • Tretinoin
  • Arsenic Trioxide
  • Arsenic
  • Oxides
  • Arsenicals