FLAG-ida regimen in adult R/R AML patients – An Italian study

In June 2017, in an article published in Clinical Lymphoma, Myeloma & Leukemia, Mario Delia and colleagues from the University of Bari, Bari, Italy, discussed results from their retrospective study which aimed to assess the efficacy of Fludarabine, Cytarabine, Granulocyte-Colony Stimulating Factor (GCSF) and Idarubicin (FLAG-ida) regimen as salvage therapy in order to evaluate whether variables (hematological [bone marrow (BM), peripheral blood (PB) blasts and platelets counts], time-related [duration of response and relapsed or refractory disease] and biological [molecular-risk cytogenetics]) have any prognostic impact on the outcomes of patients with Acute Myeloid Leukemia (AML).

In this study, 108 newly diagnosed AML patients (median age = 49 years) refractory (n = 66) to standard induction therapy or relapsed (n = 42) after first Complete Remission (CR) who received the FLAG-ida regimen as salvage therapy between January 2005–December 2015 at the University of Bari, were analyzed.

The key results of the study were:

• Overall Response (OR) rate; 44% (48/108)
• There was a significant positive association between OR with AML status (relapsed or refractory [P = 0.047]), molecular cytogenetic risk (P = 0.009) and platelet blasts count (P = 0.016)
• Patients who obtained a response to FLAG-ida regimen had a significantly higher Overall Survival (OS) compared to non-responders; 37 vs 11 months, P < 0.001
• There was a significant association between increased OS and allogenic transplantation; HR = 0.277, P < 0.001

Delia et al., concluded by highlighting that the results of their study show that the FLAG-Ida regimen has “value” in relapsed or refractory AML patients. They further proposed that the FLAG-ida regimen may be “used as a bridge-therapy” in AML patients awaiting allogenic transplantation.

Abstract

Primary refractory/first relapse AML patients are considered to have a worse clinical outcome post-treatment. For these patients the achievement of CR appears to be crucial in order to be able to undergo allotransplantation, maybe the only possible treatment. We used the FLAG-Ida regimen in this kind of patients as a bridge to transplant, and studied its efficacy in terms of overall response (OR) and survival (OS) rates, to assess which variables (age, LDH, bone marrow (BM), peripheral blood (PB) blasts and platelets counts, white blood cells (WBC), de novo or secondary AML, molecular-cytogentic risk, duration of response and relapsed or refractory disease), might have an impact on the outcome. We analyzed 108 consecutive adult patients (52 males, 66 females; median age 49 years, range 17-72) with newly diagnosed acute myeloid leukemia refractory to standard induction regimens or relapsed after 1stCR, who received the FLAG-Ida protocol as salvage therapy between January 2005 and December 2015. OR was achieved in 48 patients (44%) and, on multivariate analysis, variables with a positive impact on response rate were molecular-cytogenetic risk (p=0.009), duration of 1st response in relapsed AML (p=0.003), AML status (relapsed/refractory) (p=0.047) and PB blasts counts (p=0.016). In multivariate analysis, OS was significantly associated with FLAG-Ida response (HR=0.343, p=0.001) and allotransplantation (HR=0.277, p<0.001). Our data seem to confirm the value of FLAG-Ida in this setting and may suggest its best usage as bridge-therapy in patients awaiting allotransplantation.