Fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) combination therapy for elderly acute myeloid leukemia patients

Abstract

We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m 2 , days 1-4), cytarabine (1,000 mg/m 2 , days 1-4), and attenuated-dose idarubicin (5 mg/ m 2 , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F 5 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493). Am. J. Hematol. 88:10-15, 2013. V

The fludarabine, cytarabine, and granulocyte colony‐stimulating factor (FLAG) chemotherapy regimen is an alternative to anthracycline‐based therapy for the treatment of acute myeloid leukemia for patients with pre‐existing cardiac disease

“…Overall, 67% of patients achieved a CR, 17% of patients were refractory, and the mortality was 16%. Although higher CR rates have been observed in some studies, these have generally excluded patients with significant comorbidities or poor performance status . The mortality rate of 20.5% in our older cohort is somewhat higher than those reported in recent studies, for example, Lowenberg et al .…”

A prospective, multicenter phase II study of continuous infusion of FLAG for patients older than 60 yr with resistant acute myeloid leukemia: a comparison with intensive younger patients’ trial

“…The CR, CRp, and CRi were 39.3%, 9.1%, and 6.1%, respectively. These response rates are quite promising when comparing with 56.5% CR rate in modified fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) regimen in newly diagnosed elderly patients with AML . Also our response is also comparable or better than many investigational therapies although all clinical settings of each trial were not directly comparable .…”

“…Also, BM BLAST <5% at R E had a marginal significance. This implies that eradicating residual leukemia cells which are found at early evaluation after C‐FLAG could increase the possibility of CR as shown in m‐FLAI study that second induction therapy gave additional CR . Therefore, additional attenuated early reinduction therapy if there are residual leukemic cells at early evaluation could be possible option for improving CR rate.…”

American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

“…High-quality evidence showed that the risk of death was 1.17 times higher when patients 5 years younger were compared with patients 5 years older than the median age (hazard ratio [HR] [95% confidence interval per 5-year increase in age], 1.17 [1.11-1.23]). 29,56,[60][61][62][63][64][65][66][67][68][69][70][71][72] High-quality evidence showed that the risk of death was 1.72 times higher when patients with worse performance status (ECOG score of 21) were compared with those with better performance status (ECOG score of ,2) (HR [95% confidence interval], 1.72 [1.47-2.01]). 60,64,[73][74][75][76][77][78][79][80][81][82][83]123 There was also high-quality evidence showing that the risk of death was 1.59 times higher when patients with more comorbidities (HCT-CI score of 31) were compared with those with fewer comorbidities (HCT-CI score of ,3) (HR [95% confidence interval], 1.59 [1.28-1.98]).…”