Study Confirms Long-Term Safety, Efficacy of Oral Arsenic Trioxide in Patients with APL


Researchers suggested that the use of the oral agent over a prolonged period of time should now be considered part of the overall treatment plan in acute promyelocytic leukemia.

A study published in Cancer confirmed the efficacy and long-term safety of oral arsenic trioxide (As2O3) in patients with acute promyelocytic leukemia (APL).

“The main objective of this study was to define the safety, efficacy, and prognostic factors of this approach,” the authors wrote. “We further compared our data with results from 2 previous strategies to define the role of As2O3 as a maintenance therapy.”

Overall, researchers evaluated 129 consecutive adult patients with APL of all risk categories who achieved first complete remission (CR1) with conventional induction (all-trans retinoic acid [ATRA]/daunorubicin) and consolidation (daunorubicin/cytarabine [induction daunorubicin and consolidation omitted for age ≥70 years]). The study cohort then underwent maintenance comprising ATRA (45 mg/m2/day), oral As2O3 (10 mg/day), and ascorbic acid (1 g/day) (AAA) for 2 weeks every 2 months for 2 years.

Over the 17-year study period from August 1, 2002 to July 31, 2019, 63 men and 66 women were given AAA maintenance, which was already completed in 117 patients. At a median follow-up of 100 months (range, 8-215 months), 17 patients (13%) developed first relapse (R1) (hematologic, n = 14; molecular, n = 3) after a median of 19 months (range, 7-96 months) from CR1. Notably, 2 R1 patients had concomitant central nervous system (CNS) involvement.

The entire study cohort achieved CR2 with oral As2O3-based salvage. However, 5 patients had a subsequent relapse and died. Moreover, 8 patients died of unrelated causes while still on CR1.

Importantly, the 5-year and 10-year rates of relapse-free survival (RFS) were 89% and 85%, respectively. The 5-year and 10-year rates of overall survival (OS) were 94% and 87%, respectively. Even further, multivariate analysis showed that inferior RFS was correlated with FLT3-ITD (P = 0.005) and CNS involvement on presentation (P = 0.004), and inferior OS was associated with therapy-related APL (P = 0.03), FLT3-ITD (P = 0.03), and relapse (P = 0.03).

With regard to safety, the safety profile was favorable, with no grade 3/4 organ toxicities. However, a second malignancy occurred in 4 patients (3%) (breast cancer, n = 2; renal cell carcinoma, n = 1; renal pelvis transitional cell carcinoma, n = 1) after a median of 7.5 (range, 2-13) years from the diagnosis of APL. In addition, 1 patient had relapsed Graves disease 19 months after the start of AAA maintenance. Radioactive iodine was administered without interruption of maintenance though.

“About 3% of patients developed a second malignancy, suggesting that long-term follow-up and age-appropriate screening for second cancers is needed in these patients,” the authors wrote.

Moving forward, researchers indicated that with the successful incorporation of As2O3 in induction and consolidation, the use of the oral agent over a prolonged period of time should now be considered part of the overall treatment plan for patients with APL.

“When oral As2O3 is administered during induction and consolidation, the necessity of a more prolonged post-consolidation period remains to be critically appraised, particularly for a successful chemotherapy-free approach,” the authors wrote. “We are currently testing this strategy prospectively (NCT03624270).”


Gill HS, Yim R, Kumana CR, Tse E, Kwong Y. Oral Arsenic Trioxide, All-trans Retinoic Acid, and Ascorbic Acid Maintenance After First Complete Remission in Acute Promyelocytic Leukemia: Long-Term Results and Unique Prognostic Indicators. Cancer. doi: 10.1002/cncr.32937.

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