Improved Survival by Adding Lomustine to Conventional Chemotherapy for Elderly Patients With AML Without Unfavorable Cytogenetics: Results of the LAM-SA 2007 FILO Trial

Abstract

Purpose Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. Patients and Methods Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC]). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. Results From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% ( P = .01). The proportional hazards assumption was rejected for OS ( P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively ( P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm ( P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm ( P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm ( P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm ( P = .04), and fewer patients required a second treatment after ICL. Conclusion Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.

Low-intensity regimens versus standard-intensity induction strategies in acute myeloid leukemia

“…3 In addition, elderly patients often present comorbidities and reduced functional reserves, which are associated with increased treatment-related mortality and represent contraindications to the use of intensive chemotherapy (ICT). Consequently, population-based studies have shown that 50% to 70% of elderly patients are not offered ICT, [4][5][6] and those few that are eligible have a generally better outcome [7][8][9] when compared with those deemed unfit for ICT with a median overall survival (OS) of 12 months versus 3 to 10 months, respectively. [10][11][12] However, there have been several advances during the past decade that attempt to address this issue, such as the optimization of ICT regimens 8 and the use of nonmyeloablative conditioning regimens for allogeneic stem cell transplantation (SCT), 13 while the development of therapies utilizing hypomethylating agents (HMAs) has provided an effective alternative to ICT.…”

Outcome of patients aged 60‐75 years with newly diagnosed secondary acute myeloid leukemia: A single‐institution experience

“…Lomustine is an alkylating agent with anti‐leukemic activity . The FILO study group recently reported the significant impact of adding lomustine to idarubicin and cytarabine with a higher response rate and reduction in relapses resulting in better EFS and improved OS . Furthermore, we have been using idarubicin over 5 days for a long time in both younger and older patients based on the pharmacologic properties of this drug .…”

“…Obviously, our study has several limitations to make definitive general conclusions. It was retrospective, monocentric and we recognize that our chemotherapy regimen is not broadly used outside centers from the French Innovative Leukemia Organization (FILO) study group . Moreover, despite the selection criteria of CPX‐351 trial, there were significant differences between both studies especially regarding prior exposure to HMA, which should be kept in mind for interpretation of data.…”

“…Median EFS, RFS and OS were 7 (IQR, 3-16), 8 (4-28), and 11 (5-29) months, respectively ( Figure 1). OS was 21% [95%CI: [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and 17% [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] at 3 and 5 years, respectively. In allografted patients, median OS starting from allogeneic stem cell transplantation was 15 months (5-NR) whereas 3-year and 5-year OS were 50% [95%CI: .…”

“…After censoring patients at the date of allogeneic stem cell transplantation, OS at 5 years was 14% [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and 2% [0.2-9.3], in patients treated by intensive chemotherapy and HMA, respectively. In patients aged ≥ 70 years at diagnosis, OS at 5 years was 11% and 3% [0.3-14.3], in patients treated by intensive chemotherapy and HMA, respectively; whereas in patients aged < 70 years, OS at 5 years was 19% [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and 0%, in patients treated by intensive chemotherapy and HMA, respectively.…”