Addition of Lomustine (CCNU) to Induction and Post-Remission Chemotherapy for Fit Elderly AML Patients without Unfavorable Cytogenetics: Results of the Lamsa-2007 Goelams Trial

Background: The treatment of Acute Myeloid Leukemia (AML) in elderly patients remains unsatisfactory, with an expected survival time of about 1 year post diagnosis. In an attempt to improve outcome for these patients, the prospective open-label phase 3 LAMSA-2007 trial (Clinicaltrial.gov ID, NCT00590837) repeated, at decreasing doses in consolidation and reinduction courses, a standard induction regimen with cytarabine and idarubicin (IC), with or without the randomized addition of lomustine (ICL). This alkylating agent with significant anti-leukemic activity is widely used in France for AML therapy. This study was performed as a confirmatory trial, following our previous report of the French experience in which this compound stood out as a favorable factor of improved outcome for patients with non-unfavorable cytogenetics (Pigneux, JCO 2010). Methods: Eligible patients were adults 60 years old or more, with previously untreated AML, fit to receive intensive chemotherapy (ECOG and SORROR Results: From February 2008 to December 2011, 459 patients were enrolled and 424 were evaluable. The median age of analyzed patients was 68 yo (60-81), 58% were male. Cytogenetics was favorable (5.2%), intermediate (90.3%) or failure (4.5%). Overall, 26% of the patients had a favorable genotype based on NPM, CEBPa and FLT3 ITD mutational status. The two arms were comparable for pre-treatment characteristics. There were 3.7% induction deaths in the IC arm and 7.7% in the ICL arm (p=0.11). The rate of primary resistant AML was 21.4% after IC versus 7.7% after ICL (p Conclusion: Thisschedule using the same drugs at decreasing doses during induction, consolidation and reinductions provided unusually good results in the IC arm, further improved in the ICL arm by the addition of lomustine, in fit elderly AML patients without unfavorable cytogenetics, with acceptable toxicity. The higher rate of CR, reduced relapse incidence and improved EFS in the ICL arm support the anti-leukemic effect of lomustine in elderly AML patients, even if it does not translate in a significantly prolonged long term overall survival. New strategies for maintenance therapy remain to be improved in this setting to sustain this positive effect. Disclosures Vey: Janssen: Honoraria; Roche: Honoraria; Celgene: Honoraria.