[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).
【中文摘要】
隨著全反式維甲酸（ATRA）和三氧化二砷（ATO）在治療急性早幼粒細胞白血病（APL）中的廣泛應用，減少毒副反應成為APL治療的研究熱點。本研究針對不同危險分層的APL患者，擬評估ATO是否可以替代或減少化療。所有患者在接受ATRA聯合ATO為基礎的誘導治療並獲得完全緩解後，按1:1被隨機分配至ATO組或非ATO組進行鞏固治療：低/中危患者分別接受ATRA-ATO或ATRA-蒽環類化療；高危患者分別接受ATRA-ATO-蒽環類化療或ATRA-阿糖胞苷-蒽環類化療。主要研究終點是3年無病生存（DFS），預設的非劣效性界值為-5%。研究共納入855例患者，中位隨訪54.9個月，最終755例隨機患者中有658例可進行隨訪滿3年的評估。在ATO組中，96.1%（319/332）的患者獲得3年DFS，非ATO組為92.6%（302/326），差值為3.45%（95%CI -0.07~6.97），證實非劣效性（P<0.001）。採用Kaplan–Meier方法，ATO組7年DFS為95.7%（95%CI 93.6~97.9），非ATO組為92.6%（95%CI 89.8~95.4，P=0.066）。次要終點中，ATO組7年累積復發率為2.2% （95%CI 1.1~4.2），顯著低於非ATO組（6.1% [95%CI 3.9~9.5]，P=0.011）。鞏固治療期間，ATO組的3至4級血液學不良反應顯著降低。因此，本研究說明在鞏固階段使用ATRA聯合ATO替代或減少化療非劣於ATRA聯合化療方案。(https://www.clinicaltrials.gov/，註冊號：NCT01987297)