Risk factors for induction failure of standard chemotherapy with anthracycline and cytarabine in Acute Myeloid Leukemia Patients

Abstract

Induction therapy (IT) with anthracycline and cytarabine (DA) is, despite a new era with targeted therapies such as FLT-3- or IDH-1/2- inhibitors, still the backbone of treatment for acute myeloid leukemia (AML). In this retrospective study we investigated possible risk factors for induction failure (IF) in 109 AML-patients, who were consecutively treated between 2013 and 2018 at our institution. We evaluated all patients at diagnosis for CMV IgG-status, LDH-value, platelet count, blast count in bone marrow (BM), Sorror comorbidity score (range 0-6), age (>70 years), cytogenetic risk factors according to the ELN classification (favourable [n=15], intermediate [n=56], or high risk [n=38]), occurrence of biclonal AML detected by flow cytometry and extramedullary AML-manifestation. In 43 (39%) patients an IF was observed. 38 of these patients went on to received a salvage therapy with idarubicin and fludarabine (n=30) or directly to allotransplant (n=8), whereas 5 patients received only best supportive care. Only age >70-years (p=0.020, odds ratio [OR] 2.5), cytogenetic adverse risk classification (p=0.014; OR 3.21), Sorror comorbidity score of >2, (p=0.019, OR 2.72), and > 40% blasts in BM (p=0.004; OR 3.64), had influence on the occurrence of IF after DA. Patients with IF or adverse cytogenetics and without subsequent transplant had a worse prognosis (2-year OS for IF 19.4% + 16.8% versus 86.9% + 7.6%, p=0.0001). In multivariate analyses for OS only transplantation (HR 0.37; [95% CI 0.19-0.76], p=0.007) and blasts >40% in BM (HR 2.24, [95% CI 1.07 – 4.68], p= 0.032), but not IF were identified as independent risk factors.