Lenalidomide Is Active in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) Carrying Unfavorable Chromosomal Abnormalities.

Abstract

Genomic abnormalities, according to the Dohner hierarchical classification, are an important prognostic factor in chronic lymphocytic lymphoma (CLL). Specific chromosomal aberrations, such as a deletion 17p (P53 abnormalities) and deletion 11q (ATM defects), are associated with aggressive disease and inferior response to purine analogue-based chemotherapy. Lenalidomide is an immunomodulatory agent that has demonstrated clinical efficacy in patients with relapsed or refractory CLL in 2 separate phase II clinical trials (Chanan-Khan et al. JCO 2006; Ferrajoli et al. Blood 2006 abst). To investigate the clinical activity of lenalidomide in patients with high-risk cytogenetics (17p or 11q abnormalities), we reviewed data from 2 clinical studies. On these studies, lenalidomide was given orally either at 10 mg daily for 28 days followed by 5 mg increments every 28 days to a maximum dose of 25 mg (study A) or given at 25 mg on day 1–21 of each 28 day cycle (study B). The presence of deletion 17p or deletion 11q was demonstrated by interphase fluorescence in situ hybridization (FISH) analysis. Clinical responses were assessed using the NCI-WG 1996 criteria. Among the 80 patients treated, 40 patients with deletion 17p or deletion 11q were identified. Their characteristics are described in Table 1. The overall response rate in patients carrying deletion 17p or 11q was 35% (14/40) and responses are depicted in Table 2. Median response duration was 12 months in both studies. Based on our experience, single agent lenalidomide induces complete and partial responses in patients with unfavorable genomic aberrations, a group characterized by a poor outcome in several studies. The activity of this agent warrants further evaluation in this patient population. Table 1. Characteristics of 40 patients with unfavorable cytogenetics Study A Study B N=24 N=16 Median age, years (range) 63 (49–86) 62 (56–75) Rai stage III/IV 13 (54%) 4 (25%) Median no. of prior therapies (range) 3 (1–15) 3 (1–10) Median beta 2 microglobulin (range) 4.5 (1.9–10.1) 4 (2–10) Table 2. Responses according to NCI-WG criteria in 40 patients with unfavorable cytogenetics. Response Study A Study B 17p- (N=8) 11q- (N=16) 17p-/11q- (n=24) 17p- (N=6) 11q- (n=10) 17p-/11q- (N=16) CR, n 0 2 2 0 1 1 PR, n 1 4 5 3 3 6 OR, n (%) 1 (13) 6 (38) 7 (29) 3 (50) 4 (40) 7 (44)