Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial

A Bühler, C-M Wendtner, T J Kipps, L Rassenti, G A M Fraser, A-S Michallet, P Hillmen, J Dürig, S A Gregory, M Kalaycio, T Aurran-Schleinitz, L Trentin, J G Gribben, A Chanan-Khan, B Purse, J Zhang, S De Bedout, J Mei, M Hallek, S Stilgenbauer, A Bühler, C-M Wendtner, T J Kipps, L Rassenti, G A M Fraser, A-S Michallet, P Hillmen, J Dürig, S A Gregory, M Kalaycio, T Aurran-Schleinitz, L Trentin, J G Gribben, A Chanan-Khan, B Purse, J Zhang, S De Bedout, J Mei, M Hallek, S Stilgenbauer

Abstract

Efficacy of lenalidomide was investigated in 103 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated on the prospective, multicenter randomized phase-II CLL-009 trial. Interphase cytogenetic and mutational analyses identified TP53 mutations, unmutated IGHV, or del(17p) in 36/96 (37.5%), 68/88 (77.3%) or 22/92 (23.9%) patients. The overall response rate (ORR) was 40.4% (42/104). ORRs were similar irrespective of TP53 mutation (36.1% (13/36) vs 43.3% (26/60) for patients with vs without mutation) or IGHV mutation status (45.0% (9/20) vs 39.1% (27/68)); however, patients with del(17p) had lower ORRs than those without del(17p) (21.7% (5/22) vs 47.1% (33/70); P=0.049). No significant differences in progression-free survival and overall survival (OS) were observed when comparing subgroups defined by the presence or absence of high-risk genetic characteristics. In multivariate analyses, only multiple prior therapies (⩾3 lines) significantly impacted outcomes (median OS: 21.2 months vs not reached; P=0.019). This analysis indicates that lenalidomide is active in patients with relapsed/refractory CLL with unfavorable genetic profiles, including TP53 inactivation or unmutated IGHV. (ClinicalTrials.gov identifier: NCT00963105).

Conflict of interest statement

C-MW receives research funding, consultancy and honoraria by Celgene; MH receives research support from Celgene; TJK has served as an advisor to Celgene and received research funding from Celgene; GAMF has received honoraria from Celgene; PH receives honoraria from Celgene; JD has received a research grant and honoraria from Celgene; JGG receives honoraria from Celgene, Roche, Pharmacyclics, Mundipharma and Abbvie, and has received research support grant funding from Celgene; BP is an employee of Celgene and has equity; JZ is an employee of Celgene and has equity; SDB is an employee of Celgene and has equity; JM is an employee of Celgene and has equity; SS has received a research grant and honoraria from Celgene; the remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Progression-free survival curves. Patients with and without (a) TP53 mutations; (b) IGHV mutations; (c) del(11q); and (d) del(17p).

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