Alternative Effective and Safe Induction Regimens for Newly Diagnosed Acute Myeloid Leukemia in Patients with Cardiac Contra-indication to Anthracyclines

Abstract Introduction: The standard first line treatment for acute myeloid leukemia (AML) is a combination of cytarabine and anthracyclines. To date, there is no consensual regimen for patients who are ineligible because of cardiac comorbidities or prior exposure to anthracyclines. Methods: 52 newly diagnosed or relapsed/refractory (R/R) AML patients were treated intensively in 3 French centers. All patients had at least one contra-indication to receive anthracyclines. 3 types of regimen were used: fludarabine, cytarabine and G-CSF (FLAG), clofarabine and cytarabine (CLARA) and topotecan plus cytarabine (TA). Results: 30 (58%) patients had de novo AML. ELN 2013 risk categories were favorable, intermediate and adverse in 4 (8%), 27 (52%) and 20 (39%) patients, respectively. 24 patients received TA and 28 patients FLAG/CLARA regimens. 50% of the patients. had cardiac dysfunction and 50% prior anthracycline exposure above MTD. The rate of cardiac events was similar after TA (17%) and FLAG/CLARA (25%, p=0.78). The 5-year NRM was 17,9% and 12,5% in the TA and FLAG/CLARA groups respectively (p value= 0,59). In patients with previously untreated AML, CR rate was 18/25 (72%) but the median overall survival (OS) was only 9.7 months Conclusion: TA, FLAG and CLARA regimens are efficient and associated with acceptable toxicity in AML patients ineligible for "3+7" regimen due to cardiac comorbidities. However, long term outcome remains disappointing highlighting the need for the development of less toxic regimens.