The FOSSIL Study: FLAG or standard 7+3 induction therapy in secondary acute myeloid leukemia. (July 2018)

• Record Type: Journal Article
• Authors: Vulaj, Vera; Perissinotti, Anthony J.; Uebel, James R.; Nachar, Victoria R.; Scappaticci, Gianni B.; Crouch, Ashley; Bixby, Dale L.; Burke, Patrick W.; Maillard, Ivan; Talpaz, Moshe; Marini, Bernard L.
• Is Part Of: Leukemia research. Volume 70(2018)
• Page Start: 91
• Page End: 96
• Publication Date: 2018-07
• Subjects: Secondary acute myeloid leukemia -- sAML -- FLAG -- 7 + 3 -- CPX-351; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2018.05.011
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: FLAG induction produces 70% overall response rates in secondary AML. Induction mortality rate was 3% and duration of neutropenia was shorter with FLAG. FLAG induction allowed half of all patients to proceed to consolidation therapy. FLAG represents a highly effective, lower-cost approach to treating secondary AML. Abstract: 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.