Clofarabine in previously untreated elderly (>65 yrs) AML patients with an unfavourable cytogenetic profile who are considered unfit for standard intensive chemotherapy

Abstract

6513 Background: Elderly AML patients (>65 yrs) are a very poor prognostic population. Standard treatment achieves an 18% overall response (OR) rate (low dose Ara-C, U.K. AML 14 trial) with no little or no responses observed in high-risk cytogenetic patients. BIOV-121 is a Phase II non-randomized study of clofarabine, a novel, next generation purine nucleoside analogue, in older patients (>65 yrs) with previously untreated acute myeloid leukemia (AML) for whom standard intensive chemotherapy is not considered suitable. Methods: 66 patients aged > 65 yrs with untreated AML were enrolled in study BIOV-121. All patients were considered unfit for standard intensive chemotherapy based primarily on age (> 65 years) and/or performance status. All patients received clofarabine 30mg/m2 for 5 consecutive days repeated every 28 days (1 course) for a maximum of 6 courses. The primary study endpoint was overall response rate (ORR) defined as the number of patients achieving a CR, CRi, or PR according to the international working group guidelines. A preliminary analysis was conducted on both patients with an unfavourable cytogenetic profile (11/44 patients), for whom data was available, and on patients > 70 years of age (36/66 patients). Unfavourable cytogenetic prognostic risk was defined as the presence of a complex karyotype, monosomies of chromosome 5 (del [5q]/5q-), or 3q abnormalities as reported by Grimwade et al (U.K. MRC AML 10 trial). Results: Of 44 patients for whom cytogenetic data was available, 25% (11/44) had an unfavourable cytogenetic prognostic risk profile. The median number of clofarabine courses administered in this patient group was one. With a median age of 68 years the overall response rate (ORR) in this unfavourable cytogenetic patient group was 36% (4/11) with a 27% complete response (CR) rate. 55% (36/66) of patients were aged >70 years. The ORR and CR rate was 56% and 44% respectively in patients aged >70 years. The toxicity of clofarabine was acceptable and manageable in elderly AML patients. Conclusions: Clofarabine appears superior to current standard treatment (low-dose Ara-C) in both unfavourable cytogenetic AML (>65 years) and AML patients > 70 years (all cytogenetic risk groups). [Table: see text]