The FOSSIL Study: FLAG or standard 7+3 induction therapy in secondary acute myeloid leukemia
Vulaj V, Perissinotti AJ, Uebel JR, Nachar VR, Scappaticci GB, Crouch A, Bixby DL, Burke PW, Maillard I, Talpaz M, and Marini BL. The FOSSIL Study: FLAG or standard 7+3 induction therapy in secondary acute myeloid leukemia Leuk Res 2018; 70:91-96.
Patients with secondary acute myeloid leukemia (sAML) have poor outcomes, with CR/CRi rates of 25-35% with standard 7 + 3 induction chemotherapy, while single center non-comparative analyses suggest promising outcomes with FLAG. We conducted a single-center, retrospective cohort study assessing outcomes in treatment-naïve patients with sAML treated with fludarabine, high-dose cytarabine, and granulocyte colony-stimulating factor (FLAG, n = 40) compared with 7 + 3 (n = 66). Median patient age was 63 years (range: 27-82) in the FLAG group and 60 years (range: 21-76) in the 7 + 3 group (P = 0.968). Patients treated with FLAG achieved higher overall response rates (CR + CRi + MLFS) compared to 7 + 3 (70% vs. 48%, P = 0.043). FLAG was well tolerated, with only one induction death (30-day mortality rate, 3% vs. 8%, P = 0.405) and no cases of cerebellar toxicity. Duration of neutropenia was significantly shorter with FLAG (median 16 vs. 23 days, P < 0.001). Half of the FLAG-treated patients proceeded to consolidative therapy compared with only 27% of those who received 7 + 3 (P = 0.022). Overall survival was comparable between groups (8.5 mos, FLAG vs. 9.1 mos, 7 + 3; P = 0.798). Thus, FLAG may represent a low-cost treatment strategy in sAML that produces higher response rates and promising survival outcomes with minimal treatment-related toxicity. Further studies are required to prospectively compare FLAG to the newly FDA-approved CPX-351 in sAML.
Medical Subject Headings
Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bone Marrow; Female; Humans; Induction Chemotherapy; Leukemia, Myeloid, Acute; Male; Middle Aged; Neoplasms, Second Primary; Prognosis; Retrospective Studies; Treatment Outcome