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1471 Impact of Arsenic Trioxide in the Treatment of Higher Risk Acute Promyelocytic Leukemia

Program: Oral and Poster Abstracts
Session: 613. Acute Myeloid Leukemias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, adult, APL, Combination therapy, Diseases, Therapies, Myeloid Malignancies, Study Population, Human
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Audrey Da Rocha1*, Bruno Cassinat, PhD, PharmD2, Mael Heiblig3*, Christian Recher, MD, PhD4*, Sarah Bertoli4*, Caroline Bonmati, MD5*, Gabrielle Roth-Guepin, MD5*, Anne Zilliox, MD6*, Marie Laloi7*, Mathilde Hunault, MD, PhD7*, Céline Berthon, MD8*, Nicolas Duployez, MD9*, Christophe Willekens, MD10*, Maria Pilar Gallego Hernanz, MD11*, Marlene Ochmann, MD12*, Thomas Cluzeau, MD, PhD13, Fatiha Chermat14*, Alexis Caulier, MD, PhD1*, Emmanuel Raffoux, M.D.15*, Pierre Fenaux, MD, PhD15, Jean Pierre Marolleau, MD, PhD16, Lionel Ades, MD, PhD17 and Delphine Lebon1*

1Hematology Department, CHU Amiens, Amiens, France
2Saint Louis Hospital, APHP, Paris, France
3Hematology Department, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
4Hematology Department, IUCT-ONCOPOLE, Toulouse, France
5Hematology Department, CHU Nancy, Nancy, France
6Hematology Department, ICANS Strasbourg, Strasbourg, France
7Hematology Department, CHU Angers, Angers, France
8Hematology Department, CHRU Lille, Lille, France
9Hematology Laboratory, CHRU Lille, Lille, France
10Hematology Department, Institut Gustave Roussy, Villejuif, France
11Hematology Department, CHU de Poitiers, Poitiers, France
12Hematology Department, CHU Orléans, Orléans, France
13CHU Nice, Nice, France
14Groupe Francophone des Myelodysplasies, Paris, France
15Hôpital Saint-Louis, Hematology Department, AP-HP, Paris, France
16Service d’Hématologie Clinique, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France
17Hôpital Saint-Louis, Hematology Department, Hopital Saint Louis, Paris, France


Acute promyelocytic leukemia (APL) accounts for 5-8% of all cases of acute myeloid leukemia (AML). The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) without chemotherapy is currently the reference treatment of standard APL (ie with baseline white blood count (WBC)<10 G/L), curing about 90% of the patients. However, the prognosis of high-risk APL (ie with WBC>10 G/L) remains more challenging, with higher rates of early death and relapse.

Here we compared the French practices for the treatment of high-risk APL patients whether patients were treated with ATRA-Chemo or ATRA-ATO according to physician decision, and evaluate the response rates, overall survival (OS) and leukemia-free survival (LFS) in the real-life settings.


ATO (in combination with ATRA) became accessible in France for the first line treatment of standard risk APL in 2012, but some patients with high-risk APL also received the same combination (generally with some form of cytoreductive chemotherapy) from that date. We retrospectively analyzed cases of high-risk APL diagnosed between 2010 and 2021 in 12 French centers, constituting a cohort of 135 patients with diagnostic of APL confirmed by cytogenetic, FISH and molecular biology assays.


Among the 135 patients with WBC>10 G/L, 88 (65%) were classified as APL variant according to FAB classification. Median age was 46 years (range 18-89) and 62 % were male. Median diagnostic WBC was 39.1 G/L (range 10-270) and median platelet count was 27 G/L (range 5-344). At diagnosis, 112 patients (83%) had hemorrhagic manifestations and disseminated intravascular coagulation (DIC) was observed in 124 patients (92%). Pulmonary and cerebral leucostasis were reported in 10 (7%) and 14 (10%) patients, respectively. Eighty-five patients received corticosteroid prophylaxis (81 (95%) with Dexamethasone and 5 (5%) with Prednisolone).

Induction therapy consisted in ATRA-ATO for 50 patients (38%) while 85 patients (62%) were treated with ATRA combined with chemotherapy (anthracycline and cytarabin) but without ATO. All patients treated with ATO were cytoreduced: 7 with Hydroxyurea (14%), 17 with Idarubicin (34%) and 26 with both (52%). 29 patients treated without ATO during induction were cytoreduced with Hydroxurea (34%).

Most patients experienced one or more adverse events during induction, including sepsis (49 in the ATO group versus 71 in the non ATO group, 98% versus 83.5%, p=0.01), differentiation syndrome (20 in the ATO group versus 27 in the non ATO group, 40% versus 31.7%, p=0.33), transaminase increased (14 in ATO group versus 11 in the non ATO group, 28% versus 12.9%, p=0.03), and bleeding (7 in the ATO group versus 13 in the non ATO group, 14% versus 15.3%, p=0.8).

Following induction, 110 patients (81%) achieved complete remission (CR): 45 in the ATO group and 65 in the non ATO group (90% versus 76.4%, p=0.052). One patient (receiving ATRA with chemotherapy) was refractory, and 24 patients experienced early death (5 in the ATO group and 19 in the non ATO group, 10% versus 22.3%, p=0.069) mostly due to hemorrhage or sepsis. Median time between diagnosis and early death was 4.5 days (0-42). Relapse was observed in 6 (5.5 %) patients (5 patients treated without ATO and 1 patient with ATO during induction).

After a median follow-up of 34.6 months (0-121.1), OS at 3 years was significantly higher for the ATO group (89.9% (81.8-98.7) versus 75.1% (66.3-84.9) for the non ATO group, p= 0.035, Figure). LFS at 3 years was significantly higher for the ATO group (87.6% (78.7-97.4) versus 71.2% (62-81.7) for the non ATO group, p=0.028).


The survival outcomes were significantly poorer in high-risk APL patients treated without ATO during induction, regardless of the cytoreduction strategy. The toxicity profile of ATO was acceptable. Combining ATO and ATRA limits the use of cytotoxic chemotherapy, which could reduce myelosuppression and long-term complications such as cardiotoxicity and secondary myeloid neoplasms. Early disease-related mortality, due to haemorrhagic or infectious complications, remains the major issue for these patients but tend to be reduced in those receiving ATRA-ATO based regiment.

This retrospective study shows that ATO-ATRA and limited chemotherapy could be a better approach than ATRA and standard intensive chemotherapy in terms of early deaths, LFS and OS.

Disclosures: Heiblig: Jazz Pharmaceuticals: Honoraria; AbbVie: Honoraria; Pfizer Inc.: Honoraria; Astellas: Honoraria; Servier: Honoraria. Bertoli: Novartis: Honoraria; Abbvie: Honoraria, Other: Travel; Astellas: Honoraria; BMS-Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria, Other: Travel; Servier: Honoraria. Cluzeau: Servier: Consultancy, Speakers Bureau; Incyte: Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Syros: Speakers Bureau; Keros: Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Raffoux: Pfizer, Inc.: Honoraria; Celgene: Honoraria; AbbVie: Honoraria; Astellas: Honoraria; Daiichi-Sankyo: Honoraria. Fenaux: Jazz: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; French MDS Group: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Ades: jazz: Honoraria; Novartis: Consultancy, Research Funding; KEROS: Consultancy; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; ROCHE: Honoraria; AMGEN: Consultancy.

*signifies non-member of ASH