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157 An Entirely Oral Regimen of Oral-Arsenic Trioxide/All-Trans Retinoic Acid/Ascorbic Acid in Newly-Diagnosed Acute Promyelocytic Leukaemia (APL): Updated Results of an Ongoing Multicentre Trial

Program: Oral and Poster Abstracts
Type: Oral
Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Novel Uses of Approved Therapeutic Agents
Hematology Disease Topics & Pathways:
Research, clinical trials, Acute Myeloid Malignancies, APL, Clinical Research, Diseases, Therapies, Myeloid Malignancies
Saturday, December 9, 2023: 2:00 PM

Harinder Gill, MD, MBBS, FRCP, FRCPath1, Rita Yim1*, Lynn Chin1*, Paul Lee1*, Vivian Li1*, Lester Au1*, Garret Man Kit Leung1*, Ka Leung Daniel Cheuk, MBBS2*, Shau-Yin Ha, MBBS3*, Chi Kong Li4, Melissa Ooi, PhD, FRCPath, MBBChir, MRCP5*, Wee-Joo Chng, MBBS, PhD, FRCPath, FRCP6, Patrick Chu, MD7*, Cyrus Kumana1* and Yok Lam Kwong, MD1*

1Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
2Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong
3Department of Paediatric and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong
4Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong
5National University Cancer Institute, Singapore, Singapore
6Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
7Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China


Pure oral arsenic trioxide (oral-ATO) solution (Arsenol ®) was first formulated in Hong Kong. It achieves a bioavailability comparable with that of intravenous ATO (i.v.-ATO). Oral-ATO combined with all-trans retinoic acid (ATRA) and ascorbic acid (the AAA regimen) combined with chemotherapy is highly efficacious in relapsed and newly-diagnosed APL. To reduce treatment-related toxicities and long-term risks of second primary cancers, a chemotherapy-free approach is increasingly favoured.


The objectives of this prospective multicentre study in newly diagnosed APL patients were: 1. to evaluate the efficacy and safety of an entirely oral AAA-induction in a risk-adapted strategy; 2. to evaluate the molecular responses during oral-AAA-based induction/consolidation/maintenance.


Newly-diagnosed APL patients were stratified by presentation leucocyte count into standard-risk (≤ 10 x 109/L) and high-risk (> 10 x 109/L) groups. Standard-risk patients and high-risk patients ≥ 65 years old received AAA induction comprising oral-ATO (Arsenol ®, Jacobson Pharma Corporation, Hong Kong) (10 mg/day, or 0.16 mg/kg in patients < 18 years old, days 1-42), ATRA (45 mg/m2/day, or 25 mg/m2/day in patients <18 years old, in 2 divided doses, days 1-42), and oral ascorbic acid (1 g/day, or 15mg/kg/day in patients <18 years old, days 1-42). High-risk patients < 65 years old received in addition daunorubicin (50 mg/m2/day i.v. for 3 days). On reaching first complete remission (CR1), consolidation with AAA (days 1-14) every 28 days for 2 cycles was given, followed by maintenance with AAA (days 1-14) every 8 weeks for 12 cycles. Real-time quantitative polymerase chain reaction for PML::RARA with a sensitivity of 10-5 was performed (weekly during induction, every 4 weeks during consolidation, every 8 weeks during maintenance and thereafter every 12 weeks for 2 years). For molecular response, the normalized copy number ratio was defined as PML::RARA copy number/ABL copy number. Primary outcomes were overall survival (OS, time from presentation to death or last follow-up), and relapse-free survival (RFS, time from CR1 to molecular or haematological relapse, death or last follow-up), and safety (according to the Common Toxicity Criteria for Adverse Events (AE) version 5.0). The secondary outcome was molecular response. Data were censored on July 22, 2023.


Between January 1, 2018 to July 22, 2023, 5 paediatric/adolescent patients (male, N=2; female, N=3) at a median age of 12 (3-15) years and 116 adult (> 18 years old) patients (male, N=47 ; female, N=69) at a median age of 49 (19-91) years were accrued (standard risk: paediatric/adolescent, N=3; adults, N=87; high-risk: paediatric/adolescent, N=2; adults, N=29). Seven patients (all high-risk adults) died at presentation before induction (intracranial haemorrhage, N=6; severe APL differentiation syndrome, DS, with leucocyte >100 x109/L, N=1). One-hundred and fourteen patients received oral-AAA-based induction (AAA alone, N=90; AAA+daunorubicin, N=24), all achieving CR1. For PML::RARA normalized copy number, all treated patients at week 8 achieved a ratio of <0.01; and on completion of AAA maintenance, all evaluable patients (N=56) achieved a ratio of <0.0001. The median follow-up was 29 (IQR: 8-47) months, with 56 patients (49%) having completed 2 years of AAA maintenance. There was only one relapse, occurring in an adult patient 12 months after completion of AAA maintenance. Molecular analysis showed a PML B2 domain A216V mutation that conferred resistance to ATO. One adult patient died of an unrelated gastrointestinal bleeding while in CR1. The 3-year OS was 99.1% (paediatric/adolescent: 100%; adult: 99%). The 3-year RFS was 97.9% (paediatric/adolescent: 100%; adult: 97.9%). The most common non-haematological AEs (all grade 1-2) were transaminitis (N=54, 47.3%) and headache (N=32, 28%) Notably, no cardiotoxicity (arrhythmias/cardiac failure) was observed. APL-DS occurred in 67 patients (58.7%) after initiation of AAA, all responding fully to intravenous dexamethasone. There were no treatment discontinuations.


The use of an entirely oral AAA-based induction in a risk-adapted strategy that minimized chemotherapy was highly effective and safe in newly-diagnosed APL of all risk categories and age groups. Early deaths remained an obstacle to realizing a cure-for-all in APL.

Disclosures: Gill: BMS: Consultancy; Pfizer: Consultancy, Other: Conference support; Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Research Funding; GSK: Consultancy; Novartis: Consultancy, Other: Conference Support, Research Funding; PharmaEssentia: Consultancy, Other: Conference Support, Research Funding. Chng: Janssen: Honoraria, Research Funding; Gilead: Honoraria; Pfizer: Honoraria; GSK: Honoraria, Research Funding; Kyan Therapetics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Mirxes: Membership on an entity's Board of Directors or advisory committees; Antengene: Research Funding; Sanofi: Honoraria; BMS: Honoraria.

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