Adding Lomustine to Conventional Chemotherapy in Older Patients With AML Without Unfavorable Cytogenetics
As reported in the Journal of Clinical Oncology by Pigneux et al, a French phase III trial (LAM-SA 2007 FILO) has shown an overall survival benefit with the addition of lomustine to conventional chemotherapy in older patients with acute myeloid leukemia (AML) without unfavorable cytogenetics.
Study Details
In the open-label trial, 424 eligible patients aged ≥ 60 years with previously untreated AML who were fit to receive intensive chemotherapy from 32 sites in the French Innovative Leukemia Organization were randomized between February 2008 to December 2011 to receive induction therapy with idarubicin and cytarabine (IC) with (ICL; n = 209) or without (n = 215) oral lomustine. Those who achieved complete response (CR) or CR with incomplete hematologic recovery (CRi) received consolidation with IC or ICL according to randomized group. The primary outcome measure was overall survival. Median age was 68 years in both groups. The database was frozen in June 2015, but follow-up was updated in May 2018.
Treatment Outcomes
CR or CRi was achieved in 84.7% of the ICL group vs 74.9% of the IC group (P = .01). The proportional hazards assumption was rejected for overall survival, indicating that treatment effect changed over time and could not be summarized using a single hazard ratio (HR). Thus, survival results were analyzed for during-induction and after-induction time periods. Death during induction occurred in 7.7% of the ICL group vs 3.7% of the IC group (HR = 1.67, P = .11). In the postinduction analysis, 2-year overall survival was 56% in the ICL group vs 48% in the IC group (HR = 0.73, P = .04). Event-free survival at 2 years was 41% vs 26% (P = .01) and cumulative incidence of relapse at 2 years was 41% vs 61% (P = .003). Post-study treatment was required in 83 patients in the ICL group and in 110 in the IC group.
Toxicity
Hematologic toxicity was greater in the ICL group, which had significantly greater median number of days of thrombocytopenia and neutropenia during both induction and consolidation. Grade 3 or 4 adverse events, primarily hematologic, occurred in 53% vs 41% of patients during induction (P = .04) and in 62% vs 52% during the entire trial (P = .04).
The investigators concluded, “Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.”
The study was supported by grants from the French National Institute of Cancer.
Arnaud Pigneux, MD, PhD, of the Hematology Clinic, Bordeaux University Hospital, is the corresponding author for the Journal of Clinical Oncology article.
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