Timed sequential therapy with high-dose cytarabine and mitoxantrone as an induction regimen for acute myeloid leukemia: An update on adverse events.

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e18524 Background: Traditionally, patients eligible for induction chemotherapy for AML are treated with the “7+3” regimen, standard doses of infusional cytarabine and an anthracycline, with historical CR rates of 50-60%. We present a retrospective analysis of an alternate induction regimen. Based on timed sequential therapy, it consists of a 2-day treatment with high dose cytarabine, which improves remission rates when used in induction, and dose intensified anthracycline therapy, which improves outcomes while maintaining an acceptable safety profile. Methods: 200 patients were treated from 2010-2015. Patients received 2 doses of cytarabine 2 gm/m2 (1.5 gm/m2 age > 70 years) IVPB over 3 hours, 12 hours apart followed by 1 dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Cytogenetics and adverse events data were collected. IWG remission criteria were used to determine remission status. Results: Median age 57.6 years (range 23-79); 105 (53%) age > 60. 119 male; 81 female. Risk stratification: 12 favorable; 108 intermediate; 80 unfavorable . Overall CR rate (CRR: CR+CRi+CRp) for all patients was 68.5%. CR rates based on risk karyotypes: favorable 100%, intermediate 76.8%, unfavorable 52.5%. Most common G3-4 adverse events: anemia (60% G3, 40% G4), neutropenia (1% G3, 99% G4), thrombocytopenia (0.5% G1, 99.5% G4). 196 patients (98%) had neutropenic fever; 134 (67%) documented infections (100 with G3/4), 62 (31%) neutropenic fever with no source. 52 (26%) experienced bleeding (15 G1, 31 G2, 4 G3, 1 G4, 1 G5). G3/4 renal or hepatic toxicity was rare. No cerebellar toxicity occurred during induction. 30 day mortality 0.5%; 60 day mortality 3%. 62 (31%) patients are still alive; 122 died, 16 lost to follow-up. Conclusions: This two-day induction regimen is an effective treatment for AML with an acceptable safety profile including patients age >60. There is a high response rate, particularly for favorable and intermediate risk karyotypes, with a low rate of early mortality. The high response rates and tolerability with this regimen provides a platform for further clinical trials to enhance outcome by combining with novel targeted therapies for AML.