The treatment of younger adult patients (< 65 years) with acute myeloid leukemia (AML) with induction chemotherapy, including cytarabine (Ara-C) and an anthracycline, has high complete remission (CR) rates, however, approximately 50% of patients relapse within three years.1 The development of an effective salvage therapy for patients with relapsed or refractory (R/R) AML is therefore critical.
Dr. Nahoko Hatsumi from the Saiseikai Maebashi Hospital, Maebashi, Japan, and colleagues published a single arm, multicenter phase II study in the International Journal of Hematology evaluating the efficacy and toxicity of the FLAGM regimen in patients with R/R AML.2 Between June 2004 and February 2008, enrolled patients (n = 41; median age = 52 years; range, 18–64) received the FLAGM regimen, consisting of filgrastim (G-CSF; 300 µg/m2; subcutaneous; at start of regimen and every 24 h thereafter; total doses = 4), fludarabine (15 mg/m2; 30 min infusion; 20 h after start of regimen; every 12 h thereafter; total doses = 8), Ara-C (2 g/m2; 3 h infusion; 4 h after start of fludarabine; every 12 h, total doses = 8), and mitoxantrone (10 mg/m2; daily; 30 min infusion with Ara-C; at 72, 96, and 120 h after regimen start). The primary endpoint of this study was the CR rate following one course of therapy.
- Median follow-up: 33 months (range, 4–46)
- Primary study endpoint was met, with CR rate in all evaluable patients of 73% (95% CI, 58–84)
- CR rate in primary refractory patients: 50%
- CR rate in patients in first relapse: 78% (95% CI, 61–89)
- CR rate in patients refractory to salvage therapy following first relapse: 100%
- Patients receiving allogeneic stem cell transplantation (SCT) following FLAGM regimen: 80% (33/41)
- For patients who achieved a CR following FLAGM regimen, 80% (24/30) received SCT during CR
- For all evaluable patients, the 2-year overall survival rate: 39.4% (95% CI, 25.2–55.6)
- For patients achieving a CR (n = 30), the 2-year relapse-free survival rate: 43.5% (95% CI, 26.7–61.9)
- All patients experienced grade IV leukopenia and thrombocytopenia
- One early death occurred due to pneumonia within 30 days, all other patients recovered
- The most common grade III/IV adverse events include: nausea/vomiting (15%), diarrhea (7%), elevated liver enzymes (7%), stomatitis (2%), and pyrexia (2%)
- During the follow-up period, a total of 26 deaths occurred
The study investigators concluded that this phase II study showed the FLAGM was an effective and safe salvage therapy option for patients with R/R AML. In addition to this, the authors also demonstrated that the FLAGM regimen enabled a high proportion of patients to receive SCT.