Acute Promyelocytic Leukemia Asian Consortium study of arsenic trioxide in newly-diagnosed patients: impact and outcome

• In APL, frontline oral or intravenous arsenic trioxide (ATO) reduced early deaths and improved RFS and OS, independent of risk category.

• Without frontline ATO, inferior RFS could still be mitigated by using an oral-ATO-based regimen in maintenance.

The Acute Promyelocytic Leukemia Asian Consortium analyzed a contemporaneous cohort of newly-diagnosed APL patients treated with and without frontline arsenic trioxide (ATO) in six centers. The objectives were to define the impact of ATO on early deaths and relapses, and its optimal positioning in the overall treatment strategy. In a 21.5-year period, 324 males and 323 females at a median age of 45.5 (range: 18.1-91.8) years (low/intermediate risk, N=448; high-risk, N=199) were treated. Regimens included frontline all-trans retinoic acid (ATRA)/chemotherapy and maintenance with/without ATO (N=436); ATRA/intravenous-ATO/chemotherapy (ATRA/i.v.-ATO; N=61); and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; N=150). The ATRA/chemotherapy group, compared with the ATO-containing (ATRA/i.v.-ATO and oral-AAA) groups, had significantly more frequent early deaths within 60 days (8.3% versus 3.3%; P=0.05); inferior 60-day survival (91.7% versus 98.4%/96%; P<0.001); inferior 5-year relapse-free survival (RFS) (76.9% versus 92.8%/97.8%; P<0.001) and inferior 5-year overall survival (OS) (84.6% versus 91.4%/92.3%; P=0.03). Addition of oral-ATO maintenance could partly mitigate the inferior 5-year RFS resulting from omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance versus ATRA/chemotherapy/ATO maintenance versus ATRA/i.v.-ATO versus oral-AAA: 71.1% versus 87.9% versus 92.8% versus 97.8%, P<0.001). The favorable survival impacts of ATO were observed in both low/intermediate-risk and high-risk patients, so that conventional risks (high leucocyte and low platelet counts) were overcome. Therefore, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. Its benefits were most obvious in frontline treatment, but were still observed during maintenance. (ClinicalTrials.gov Identifier: NCT04251754)