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Alternative Effective and Safe Induction Regimens for Newly Diagnosed Acute Myeloid Leukemia in Patients With Cardiac Contraindication to Anthracyclines.
Clin Lymphoma Myeloma Leuk. 2019 Nov 26 [Online ahead of print]CL

Abstract

INTRODUCTION

The standard first-line treatment for acute myeloid leukemia (AML) is a combination of cytarabine and anthracyclines. To date, there is no commonly agreed-on regimen for patients who are ineligible for this therapy because of cardiac comorbidities or prior exposure to anthracyclines. We compared 3 anthracycline-free regimens currently used in France.

PATIENTS AND METHODS

Two patients with newly diagnosed or relapsed/refractory AML were treated intensively in 3 French centers. All patients had at least one contraindication to the receipt of anthracyclines. Three regimen types were used: fludarabine, cytarabine, and granulocyte-colony stimulating factor (FLAG); clofarabine and cytarabine (CLARA); and topotecan plus cytarabine (TA).

RESULTS

Thirty patients (58%) had de novo AML. The European LeukemiaNet 2013 risk categories were favorable, intermediate, and adverse in 4 (8%), 27 (52%), and 20 (39%) patients, respectively. Twenty-four patients received TA and 28 FLAG/CLARA regimens. Fifty percent of patients had cardiac dysfunction, and 50% had prior anthracycline exposure above the maximum tolerated dose. The rate of cardiac events was similar after TA (17%) and FLAG/CLARA (25%) (P = .78). The 5-year nonrelapse mortality was 17.9% and 12.5% in the TA and FLAG/CLARA groups, respectively (P = .59). In patients with previously untreated AML, complete response occurred in 18 (72%) of 25, but median overall survival was only 9.7 months.

CONCLUSION

TA, FLAG, and CLARA regimens are efficient and are associated with acceptable toxicity in AML patients ineligible for the 3 + 7 regimen as a result of cardiac comorbidities. However, long-term outcome remains disappointing, thereby highlighting the need for the development of less toxic regimens.

Authors+Show Affiliations

CHU of Nice, Hematology Department, Cote D'Azur University, Nice Sophia Antipolis University, Nice, France; CHU of Nice, Oncohematology Laboratory, Cote D'Azur University, Nice Sophia Antipolis University, Nice, France.Hematology Department, Paoli-Calmettes Institute, Marseille, France.Oncology Department, Antoine Lacassagne Center, Nice, France.CHU of Nice, Hematology Department, Cote D'Azur University, Nice Sophia Antipolis University, Nice, France.Hematology Department, Paoli-Calmettes Institute, Marseille, France.Hematology Department, Paoli-Calmettes Institute, Marseille, France.Hematology Department, Paoli-Calmettes Institute, Marseille, France.Hematology Department, Paoli-Calmettes Institute, Marseille, France.CHU of Nice, Oncohematology Laboratory, Cote D'Azur University, Nice Sophia Antipolis University, Nice, France.Department of Clinical Hematology, Paoli-Calmettes Institute, Marseille, France.CHU of Nice, Hematology Department, Cote D'Azur University, Nice Sophia Antipolis University, Nice, France; INSERM U1065, Mediterranean Center of Molecular Medecine, Cote D'Azur University, Nice, France. Electronic address: cluzeau.t@chu-nice.fr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31865004

Citation

Marcault, Clemence, et al. "Alternative Effective and Safe Induction Regimens for Newly Diagnosed Acute Myeloid Leukemia in Patients With Cardiac Contraindication to Anthracyclines." Clinical Lymphoma, Myeloma & Leukemia, 2019.
Marcault C, Venton G, Gastaud L, et al. Alternative Effective and Safe Induction Regimens for Newly Diagnosed Acute Myeloid Leukemia in Patients With Cardiac Contraindication to Anthracyclines. Clin Lymphoma Myeloma Leuk. 2019.
Marcault, C., Venton, G., Gastaud, L., Mannone, L., Rey, J., D'Incan, E., Saillard, C., Charbonnier, A., Raynaud, S., Vey, N., & Cluzeau, T. (2019). Alternative Effective and Safe Induction Regimens for Newly Diagnosed Acute Myeloid Leukemia in Patients With Cardiac Contraindication to Anthracyclines. Clinical Lymphoma, Myeloma & Leukemia. https://doi.org/10.1016/j.clml.2019.11.016
Marcault C, et al. Alternative Effective and Safe Induction Regimens for Newly Diagnosed Acute Myeloid Leukemia in Patients With Cardiac Contraindication to Anthracyclines. Clin Lymphoma Myeloma Leuk. 2019 Nov 26; PubMed PMID: 31865004.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alternative Effective and Safe Induction Regimens for Newly Diagnosed Acute Myeloid Leukemia in Patients With Cardiac Contraindication to Anthracyclines. AU - Marcault,Clemence, AU - Venton,Geoffroy, AU - Gastaud,Lauris, AU - Mannone,Lionel, AU - Rey,Jerome, AU - D'Incan,Evelyne, AU - Saillard,Colombe, AU - Charbonnier,Aude, AU - Raynaud,Sophie, AU - Vey,Norbert, AU - Cluzeau,Thomas, Y1 - 2019/11/26/ PY - 2019/07/16/received PY - 2019/11/04/revised PY - 2019/11/19/accepted PY - 2019/12/23/entrez PY - 2019/12/23/pubmed PY - 2019/12/23/medline KW - AML KW - Adverse KW - Clofarabine KW - Comorbidities KW - Topotecan JF - Clinical lymphoma, myeloma & leukemia JO - Clin Lymphoma Myeloma Leuk N2 - INTRODUCTION: The standard first-line treatment for acute myeloid leukemia (AML) is a combination of cytarabine and anthracyclines. To date, there is no commonly agreed-on regimen for patients who are ineligible for this therapy because of cardiac comorbidities or prior exposure to anthracyclines. We compared 3 anthracycline-free regimens currently used in France. PATIENTS AND METHODS: Two patients with newly diagnosed or relapsed/refractory AML were treated intensively in 3 French centers. All patients had at least one contraindication to the receipt of anthracyclines. Three regimen types were used: fludarabine, cytarabine, and granulocyte-colony stimulating factor (FLAG); clofarabine and cytarabine (CLARA); and topotecan plus cytarabine (TA). RESULTS: Thirty patients (58%) had de novo AML. The European LeukemiaNet 2013 risk categories were favorable, intermediate, and adverse in 4 (8%), 27 (52%), and 20 (39%) patients, respectively. Twenty-four patients received TA and 28 FLAG/CLARA regimens. Fifty percent of patients had cardiac dysfunction, and 50% had prior anthracycline exposure above the maximum tolerated dose. The rate of cardiac events was similar after TA (17%) and FLAG/CLARA (25%) (P = .78). The 5-year nonrelapse mortality was 17.9% and 12.5% in the TA and FLAG/CLARA groups, respectively (P = .59). In patients with previously untreated AML, complete response occurred in 18 (72%) of 25, but median overall survival was only 9.7 months. CONCLUSION: TA, FLAG, and CLARA regimens are efficient and are associated with acceptable toxicity in AML patients ineligible for the 3 + 7 regimen as a result of cardiac comorbidities. However, long-term outcome remains disappointing, thereby highlighting the need for the development of less toxic regimens. SN - 2152-2669 UR - https://www.unboundmedicine.com/medline/citation/31865004/Alternative_Effective_and_Safe_Induction_Regimens_for_Newly_Diagnosed_Acute_Myeloid_Leukemia_in_Patients_With_Cardiac_Contraindication_to_Anthracyclines L2 - https://linkinghub.elsevier.com/retrieve/pii/S2152-2650(19)32167-6 DB - PRIME DP - Unbound Medicine ER -