Intensive (2+5) Or Semi-Intensive (FLUGA) Chemotherapy For Patients With Acute Myeloid Leukemia Who Are 70 Years Of Age Or Older

Abstract

Introduction Intensive chemotherapy in patients with acute myeloid leukemia (AML) who are 70 years of age or older leads to an overall survival (OS) lower than 30% at one year. This is due to low tolerability of intensive chemotherapy schedules and biological adverse features of this group of patients. Objectives To evaluate the therapeutic results in AML patients who are 70 years of age or older treated with intensive (2+5) or semi-intensive (FLUGA) chemotherapy. Methods Multicenter retrospective study based on data of the epidemiologic AML PETHEMA group Registry to evaluate the OS in patients who are 70 year of age or older that have followed the treatment recommendations of the group (LMA2007/2+5 protocol: idarrubicin 12 mg/m2 for 2 days plus IV cytarabine 200 mg/m2 for 5 days, and two cycles with IV cytarabine 100 mg/m2 for 5 days; LMA2011/FLUGA protocol: 3 induction courses with oral fludarabine 40 mg/m2 for 4 days plus subcutaneous cytarabine 75 mg/m2 for 4 days following maintenance treatment with an outpatient schedule of lower doses of fludarabine plus cytarabine. Patients diagnosed with acute promyelocytic leukemia and/or an ECOG of 4 were excluded. Results Of the 155 patients included from 30 hospitals, 78 were treated according to LMA2007/2+5 scheme and 77 to LMA2011/FLUGA recommendations. Median of age in the FLUGA vs 2+5 was 77 years [70-89] vs 74 years [70-81], p<0.001; leukocytes were 27x109/L [0,6-350] vs 40 x109/L [0,4-316], p=0.13; also without significant differences in hemoglobin, platelets, fibrinogen, creatinine, albumin, uric acid and ECOG. Secondary AML affected 28% of patients in the FLUGA schedule and 26% of the 2+5; low/intermediate/high risk cytogenetics was 3%, 66% and 31% in the FLUGA schedule and 7%, 77% and 16% in the 2+5 (p=0.11). Response to induction courses following FLUGA vs 2+5 were: complete remission (CR) 51% vs 37% (p=0.13), CR plus partial remission (PR) 69% vs 47% (p=0.01), mortality 10% vs 24% (p=0.03). Hospitalization rate was 67% in the FLUGA group vs 100% in the 2+5. OS at 6 months and at 1 year were 57% and 40% with FLUGA and 48% and 24% with 2+5 (p=0.03), respectively. In addition to the therapeutic regimen, other factors associated with the OS at one year were CR vs not CR (59% vs 10%, p <0.001) and cytogenetic risk low / intermediate vs high (43% vs 0%, p <0.001). Conclusion In patients who are 70 years of age or older, therapeutic recommendations consisting in semi-intensive chemotherapy (FLUGA) led to an improved OS at 1 year compared with intensive chemotherapy (2+5). In this group of patients achieving CR should be a therapeutic goal because it significantly improves the prognosis. Disclosures: No relevant conflicts of interest to declare.

A phase 3 trial of azacitidine versus a semi‐intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia

“…Measurable residual disease (MRD) was assessed in bone marrow after cycle 9. This timepoint was selected because prior upfront PETHEMA LMA2011 guidelines recommended up to 9 cycles of FLUGA for older patients 10 . When MRD was ≥0.01%, patients continued with the same treatment (AZA or mini‐FLUGA), until relapse or progressive disease were documented.…”

“…This timepoint was selected because prior upfront PETHEMA LMA2011 guidelines recommended up to 9 cycles of FLUGA for older patients. 10 When MRD was ≥0.01%, patients continued with the same treatment (AZA or mini-FLUGA), until relapse or progressive disease were documented. Patients with MRD was <0.01% suspended treatment to enter the follow-up phase.…”

“…Since 2011, this regimen has been adopted by PETHEMA institutions as a standard treatment option for this population, and it has shown in a real-life setting an acceptable CR rate, tolerability, and 40% (95% confidence interval [CI], 30%-54%) overall survival (OS) at 1 year. 9,10 This study reports the results of an open-label, randomized, prospective, phase III, multicenter trial comparing the FLUGA versus AZA monotherapy in a large cohort of older patients aged with newly diagnosed AML.…”

“…To overcome this difficult decision making (low‐dose or intensive chemotherapy vs HMAs) in patients 65 years old or older, the Programa Español de Tratamientos en Hematología (PETHEMA) group, aiming to achieve a greater CR rate with tolerable toxicity, designed a semi‐intensive regimen with LDAC plus oral fludarabine (ie, fludarabine, cytarabine, and filgrastim [FLUGA]) to be compared with HMAs. Since 2011, this regimen has been adopted by PETHEMA institutions as a standard treatment option for this population, and it has shown in a real‐life setting an acceptable CR rate, tolerability, and 40% (95% confidence interval [CI], 30%‐54%) overall survival (OS) at 1 year 9,10 …”

Midostaurin for FLT3-mutated Acute Myeloid Leukaemia – Considerations for Optimal Use

“…In some institutions, the 5+2 regimen (5 days of cytarabine plus 2 days of an anthracycline) is preferred. 43 In these instances, it is recommended to use midostaurin on days 8 through 21 (14 days of treatment). If midostaurin is to be discontinued, the dose can be tapered or completely withdrawn, as preferred by the clinician, without the risk of a rebound effect.…”