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Observational Study
. 2025 Feb 25;9(4):862-876.
doi: 10.1182/bloodadvances.2024014999.

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

Harinder Gill  1 , Radha Raghupathy  1 , Hsin-An Hou  2 , Xavier Cheng-Hong Tsai  2 , Adisak Tantiworawit  3 , Melissa G Ooi  4   5 , Gin-Gin Gan  6 , Chieh-Lee Wong  7 , Rita Yim  1 , Lynn Chin  1 , Paul Lee  1 , Vivian W K Li  1 , Lester Au  1 , Qi Zhang  1 , Garret M K Leung  1 , Tony K Y Wu  1 , Carmen Y Y Lee  1 , Wee-Joo Chng  4   5 , Hwei-Fang Tien  2   8 , Cyrus R Kumana  1 , Yok-Lam Kwong  1
Affiliations
Observational Study

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

Harinder Gill et al. Blood Adv. .

Abstract

The Acute Promyelocytic Leukemia (APL) Asian Consortium analyzed a contemporaneous cohort of newly diagnosed patients with APL treated with and without frontline arsenic trioxide (ATO) in 6 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 years (range, 18.1-91.8; 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/IV-ATO/chemotherapy (ATRA/IV-ATO; n = 61), and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; n = 150). The ATRA/chemotherapy group had significantly more frequent early deaths within 60 days (8.3% vs 3.3%; P = .05), inferior 60-day survival (91.7% vs 98.4%/96%; P < .001), inferior 5-year relapse-free survival (RFS; 76.9% vs 92.8%/97.8%; P < .001), and inferior 5-year overall survival (OS; 84.6% vs 91.4%/92.3%; P = .03) than ATO-containing groups (ATRA/IV-ATO and oral-AAA). The addition of oral-ATO maintenance partly mitigated the inferior 5-year RFS resulting from the omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance vs ATRA/chemotherapy/ATO maintenance vs ATRA/IV-ATO vs oral-AAA, 71.1% vs 87.9% vs 92.8% vs 97.8%; P < .001). The favorable survival impacts of ATO were observed in all risk groups. In conclusion, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. This trial was registered at www.clinicaltrials.gov as #NCT04251754.

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Conflict of interest statement

Conflict-of-interest disclosure: H.G. and Y.-L.K. are employees of the University of Hong Kong, which holds 2 US patents (7521071 B2 and 8906422 B2), 1 Japan patent (4786341), and 1 European patent (1562616 B1) for the use of oral-ATO in the treatment of leukemias and lymphomas. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Patient disposition, treatment characteristics and complications during induction. (A) Disposition of 647 newly diagnosed patients with APL treated with ATO-containing and non–ATO-containing regimens. Refer to the supplemental File 1 for details of treatment regimens used. (B) Trend in the distribution and number of patients treated with 4 different treatment regimens from 2001 to 2011. Refer to the supplemental File 1 for details of treatment regimens used. (C) Trends in the number and causes of early or induction deaths from 2001 to 2022. (D) Trends in the number of patients with APL-DS from 2001 to 2022. ICH, intracranial hemorrhage.
Figure 2.
Figure 2.
Impact of ATO on the outcome of newly diagnosed APL. (A) Impact of ATO-containing induction (ATRA/IV-ATO and oral-AAA) on 60-day survival compared with ATRA/chemotherapy induction. P values were .02 on univariate analysis and <.001 on multivariate analysis. (B) Impact of ATO-containing induction (ATRA/IV-ATO and oral-AAA) on RFS, compared with ATRA/chemotherapy induction. P values on both univariate and multivariate analysis were <.001. (C) Impact of ATRA/chemotherapy/ATO maintenance, ATRA/IV-ATO, and frontline oral-AAA groups on RFS compared with ATRA/chemotherapy/non-ATO maintenance. P values on both univariate and multivariate analysis were <.001. (D) Impact of ATO-containing induction (ATRA/IV-ATO and oral-AAA) on OS, compared with the ATRA/chemotherapy induction. P value was .08 on univariate analysis and .03 on multivariate analysis.
Figure 3.
Figure 3.
Other significant factors affecting outcome in newly diagnosed APL.P values shown were those obtained from univariate log-rank test. Table 2 gives the corresponding P values on multivariate Cox regression analysis. (A) Impact of CNS involvement at presentation on 60-day survival. (B) Impact of sex on post–60-day OS. (C) Impact of age on post–60-day OS. (D) Impact of therapy-related APL on post–60-day OS. (E) Impact of CNS involvement at presentation on post–60-day OS. (F) Impact of sex on RFS. (G) Impact of CNS involvement at presentation on RFS. (H) Impact of year of diagnosis on RFS. (I) Impact of age on OS. (J) Impact of APL-DS on OS. (K) Impact of CNS involvement at presentation on OS.
Figure 4.
Figure 4.
Impact of ATO on the outcome of newly diagnosed APL with different conventional risks. (A) Impact of ATO-containing induction (ATRA/IV-ATO and oral-AAA) on RFS compared with ATRA/chemotherapy induction in patients with low/intermediate-risk disease. (B) Impact of ATRA/chemotherapy/ATO maintenance, ATRA/IV-ATO, and frontline oral-AAA groups on RFS compared with ATRA/chemotherapy/non-ATO maintenance in patients with low/intermediate-risk disease. (C) Impact of ATO-containing induction (ATRA/IV-ATO and oral-AAA) on 60-day survival compared with the ATRA/chemotherapy induction in patients with high-risk disease. (D) Impact of ATO-containing induction (ATRA/IV-ATO and oral-AAA) on RFS compared with ATRA/chemotherapy induction in patients with high-risk disease. (E) Impact of ATRA/chemotherapy/ATO maintenance, ATRA/IV-ATO, and frontline oral-AAA groups on RFS compared with ATRA/chemotherapy/non-ATO maintenance in patients with high-risk disease.
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