Salvage Therapy with Flag/Idarubicin/Mylotarg (Flag-IM) Results in a Superior CR/CRp Rate and Low Toxicity When Compared to Mitoxantrone/Etoposide/Cytarabine (MEC) in Patients with Relapsed and Refractory AML.

Salvage therapy for relapsed AML has been historically unsatisfactory. Response to salvage therapy for AML was investigated using a retrospective chart review of patients at the Siteman Cancer Center who failed standard induction therapy. We identified and studied 42 patients with relapsed (N=24) or refractory (N=18) AML who received either (33/42 patients) Mitoxantrone 8mg/m², Etoposide 100 mg/m², Cytarabine 1000 mg/m² (days 1–5) (MEC) or (9/42 patients) Mitoxantrone 10 mg/m², Etoposide 100 mg/m² (days 1–5) (MV) as salvage therapy. 40/42 patients were evaluable for response by formal restaging after day +30. 13/40 entered a CR and 7/40 entered a CRp. Only 7/20 (35%) CR/CRp remained progression free with a median follow up of 5.3 months (range = 2–10 months). 6/7 who remained in CR/CRp received an allogeneic stem cell transplant and/or donor lymphocyte infusion after treatment. Median follow up for transplanted patients is 38 months with a range of 10–80 months. A similar analysis was performed on 16 patients with relapsed (N= 12) or refractory (N= 4) AML that received Fludarabine 25mg/m², Cytarabine 2000 mg/m², Idarubicin 12mg/m² (days 1–5), G-CSF 5mcg/kg (day 1+), and Gemtuzumab 9 mg/m² (day 8) (Flag-IM) for CD33+ AML. Only 15/16 patients were evaluable for response by formal restaging after day +30. Flag-IM treatment resulted in 12/15 patients achieving CR/CRp (6 CR, 6CRp). This group included 3 patients that had previously failed MEC or MV salvage therapy. 10/12 CR/CRp patients received allogeneic transplants (4 sib, 6 unrelated) and 5 (50%) are alive and disease-free with a median survival of 13.4 months (range2–27) months. In spite of a short median duration of only two months (range 1–4) from Flag-IM to allogeneic transplant, no veno-occulsive disease (0/10) was observed, and only 4/10 patients developed mild hyperbilirubinemia (range 1.3–3.8) after myeloablative conditioning for allogeneic transplant.

In conclusion, in this limited retrospective analysis, Flag-IM results in a superior CR/CRp rates when compared to MEC/MV (80% versus 50%) (p = 0.045 by 2 sided t-test) in patients with relapsed/refractory AML. Thirty day treatment related mortality after MEC/MV (2/42) and Flag-IM (1/16) were similarly low, as was VOD in patients receiving myeloablative allotransplant after Flag-IM (0/10). DFS after allogeneic transplant in those patients achieving CR/CRp after MEC/MV (6/20) and Flag-IM (4/10) (p=0.34) were similar. No patient survived greater then 10 months without allogeneic transplant. Flag-IM is an effective salvage therapy associated with acceptable toxicity in patients with relapsed refractory AML.