Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial)

Abstract

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study

“…In addition, the CIR was higher in high-risk categories than that in intermediate-risk categories, and it had no statistical difference between intermediate-and low-risk categories in our study. Similar results were obtained in the APL2012 trial (35).…”

Gene Transcription as a Therapeutic Target in Leukemia

“…The initial results of the APL0406 trial (NCT00482833) showed that the combination of ATRA and ATO is at least not inferior to standard ATRA+chemotherapy in first-line therapy of low- or intermediate-risk APL [ 166 ]. Moreover, recent studies (APL2012 trial, NCT01987297) have demonstrated that the ATRA–ATO combination in both chemotherapy-replacing and -reducing settings in consolidation is effective as a traditional ATRA–chemo combination [ 17 ].…”

“…First, the transcriptional modulators can synergize with conventional cytotoxic drugs in achieving antitumor efficacy with better tolerance, which is extremely important in children and elderly patients [ 11 , 12 ]. Second, targeting transcriptional machinery can prevent the establishment of drug resistance (NCT04017546, NCT01434316) [ 13 , 14 , 15 , 16 , 17 , 18 ]. Here, we review the fundamental aspects related to the design of tools for targeting gene transcription in hematological malignancies and analyze the current state-of-the-art in clinical trials.…”

A Network Pharmacology and Molecular Docking Strategy to Explore Potential Targets and Mechanisms Underlying the Effect of Curcumin on Osteonecrosis of the Femoral Head in Systemic Lupus Erythematosus

“…It has been widely used in the treatment of various diseases including immune diseases [19,20] and has attracted more and more attention in recent years. The Chinese medicine arsenic being found to be effective in treating leukemia is one of the best examples [21]. Curcumin, an effective monomeric component mainly extracted from the traditional Chinese medicine turmeric, has been reported to have protective effects on SLE and ONFH [22][23][24][25].…”