(003) A retrospective comparison of AML17 and APL0406 regimens for low-risk acute promyelocytic leukemia

Poster Abstract:

Background: Acute promyelocytic leukemia (APL) is an aggressive, rare and highly curable subtype of acute myeloid leukemia (AML). The two NCCN preferred category 1 regimens recommended for low-risk APL are APL0406 and AML17. Both induction regimens include all-trans-retinoic acid (ATRA) 45 mg/m2 PO daily in two divided doses. APL0406 administers arsenic trioxide (ATO) 0.15 mg/kg IV daily and AML17 administers ATO 0.3 mg/kg IV on days 1-5 of week 1 followed by 0.25 mg/kg IV twice weekly. APL0406 was used at Emory University Hospital from 2013 to 2021 until AML17 was adopted for patient convenience. Published complete remission (CR) rates are 94% and 100% for AML17 and APL0406 respectively when compared to standard chemotherapy. Currently, there are no published comparisons between AML17 and APL0406.

Objective(s): The objective of this study was to compare the efficacy and toxicity profiles of APL0406 and AML17 in patients with low-risk APL during the first four weeks of induction. The primary outcome was the mean ratio-relative dose intensity (RDI) for ATO and ATRA. Secondary outcomes included the percentage of patients requiring dose reductions or interruptions, rate of hematologic CR at the end of induction, completion of consolidation, and hospital length of stay.

Methods: This was a single-center retrospective chart review from January 1, 2013, to June 15, 2023. The mean ratio-RDI was compared using an independent two sample t-test. A sample size of 176 in each group reach was needed for 80% power to reject the null hypothesis of zero effect size when the population effect size is 0.3 and the significance level (alpha) is 0.05.

Results: Patients in the AML17 group had a 7% higher RDI of ATO compared to the APL0406 group (p=0.078). More dose reductions were observed in the AML17 group (44 vs 25%; p=0.173) and more dose interruptions were observed in the APL0406 group (45 vs 33%; p=0.301). Patients in the AML17 group had more headaches (39 vs 15%; p=0.018) and QTc prolongation (44 vs 9%; p =0.002). In both regimens, most patients achieved a hematologic CR. Other safety and efficacy outcomes did not show a statistically significant difference.

Conclusion/

Discussion: AML17 is an effective alternative to APL0406 for induction therapy in patients with low-risk APL. APL0406 may be preferred for patients with baseline QTc prolongation and history of severe headaches or migraines, as these toxicities were observed more frequently with AML17.

References (must also be included in final poster): (1) NCCN Clinical Practice Guidelines in Oncology for  Acute Myeloid Leukemia  V.3.2022. 2023.
(2) Lo-Coco F. et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. NEJM. 369(2):111-21.
(3) Burnett AK, et al. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol 2015;16(13):1295-305.