Cytogenetic correlation with efficacy on alemtuzumab (CAM) vs chlorambucil (CHLO) as front-line therapy for patients with progressive B-cell chronic lymphocytic leukemia (BCLL)

Abstract

6601 Background: CAM307, a phase III, open-label, randomized comparative trial, enrolled 297 Rai stage I-IV BCLL patients with previously untreated, progressive disease requiring treatment. Patients were randomized to treatment with CAM (n=149) vs. CHLO (n=148) using standard dosing regimens. Methods: Cytogenetic assessment was conducted prior to the start of protocol-specified therapy. Chromosomal aberrations were detected by fluorescence in situ hybridization (FISH) using specific probes. Molecular cytogenetic analyses by FISH included deletions (del) 6q21, 6q telomere, 11q22–23, 13q14–14.3 and 17p13; trisomy bands of 8q24 and 12p11.1-q11.1. Results: A total of 271 patients have been evaluated. Chromosomal aberrations were detected in 207 patients (76%) while 64 patients (24%) exhibited normal karyotype. Cytogenetic abnormalities were evaluated by response [overall response rate (ORR) and complete response (CR)] to each therapy based upon an independent response review. The comparisons of ORR and CR between treatment arms for each mutation type were calculated using the Exact method. Conclusions: Preliminarydata demonstrate a statistically significant superior response to CAM in patients with del 13q (ORR and CR) and del 11q (ORR) as well as a statistically significant superior CR to CAM in patients with normal cytogenetics. In addition, although the sample size is small, there is a trend towards a better ORR in patients with del 17p. Further exploration of CAM response rates relative to cytogenetic abnormality is warranted. [Table: see text] [Table: see text]