Arsenic, ATRA, and ascorbic acid in acute promyelocytic leukaemia maintenance

Maintenance therapy with arsenic trioxide (oral-As2O3), all-trans-retinoic acid (ATRA), and ascorbic acid in patients experiencing their first complete remission (CR1) from acute promyelocytic leukaemia (APL) was safe and resulted in excellent long-term survival.

Prof. Gill Singh (University of Hong Kong, China) pointed towards the lack of data on the long-term outcomes of patients receiving prolonged maintenance with oral-As2O3-based regimens in CR1 following non-arsenic-based induction [1]. In the current study, adult APL patients (median age 46) in CR1 (n=129) were recruited for maintenance treatment with oral-As2O3 (10 mg/day), ATRA (45mg/m²/day in 2 divided doses), and ascorbic acid (1 g/day) (AAA). AAA was administered for 2 weeks every 2 months for a total of 2 years. Prior induction treatment comprised ATRA (45 mg/m²/day in 2 divided doses for 42 days) and daunorubicin (50 mg/m²/day for 3 days). Consolidation comprised 2 monthly cycles of daunorubicin (50 mg/m²/day for 2 days) and cytarabine (100 mg/m²/day for 5 days).

The participants had a median follow-up of 100 (8-215) months, and 117 (90.1%) patients completed the full 2 years of AAA maintenance. Of these, 17 (13.2%) patients relapsed after a median of 19 (7-96) months from CR1 (morphologic relapse n=14; molecular relapse n=3). In total, 13 deaths occurred; 5 from refractory APL, and 8 patients died from unrelated causes (pneumonia n=4; acute myocardial infarction n=2; second malignancy n=2).

The 5-year and 10-year relapse-free survival rates were 88.8% and 85.1%, respectively. The overall survival was 94.2% for 5-years and 87.4% for 10-years. On univariate analysis, PML-RARA bcr3 (short) isoform (P=0.02), FLT3-ITD (P=0.005), and central nervous system involvement at diagnosis (P=0.002) were associated with worse relapse-free survival. On multivariate analysis, FLT3-ITD (P=0.005), and central nervous system involvement at diagnosis (P=0.004) were associated with worse relapse-free survival. On univariate analysis, PML-RARA bcr3 isoform (P=0.03), FLT3-ITD (P=0.01), and relapsed APL (P=0.002) were associated with worse OS. On multivariate analysis, therapy-related APL (P=0.03), FLT3-ITD (P=0.03), and relapsed APL (P=0.03) were associated with worse survival.

No serious safety signals were recorded. Grade 1 leukopenia occurred in 7 (5.4%) participants. The most common non-haematological toxicity was headache in 29.5% of the participants (Grade 1/2 n=38; Grade 3/4 n=0). Grade 1 hepatoxicity occurred in 7 (5.4%) participants and cutaneous herpes zoster infection occurred in 6 (4.7%) participants. The results of this study support using AAA as a maintenance therapy for APL patients in CR1.

1. Singh GH, et al. Abstract 3853, ASH 2019, 7-10 December, Orlando, USA.

Posted on 5 March, 202026 March, 2021