title: Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial.
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).
authors.affiliation: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bühler
authors.affiliation: Klinikum Schwabing, Academic Teaching Hospital of University of Munich, Munich, Germany.|Department I of Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: C-M
authors.initials: CM
authors.lastname: Wendtner
authors.affiliation: University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Kipps
authors.affiliation: University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Rassenti
authors.affiliation: McMaster University, Juravinski Cancer Centre, Hamilton, ON, Canada.
authors.forename: G A M
authors.initials: GA
authors.lastname: Fraser
authors.affiliation: Hospices civils de Lyon, Centre Hospitalier Lyon Sud, Lyon, France.
authors.forename: A-S
authors.initials: AS
authors.lastname: Michallet
authors.affiliation: St James's Institute of Oncology, Leeds, UK.
authors.forename: P
authors.initials: P
authors.lastname: Hillmen
authors.affiliation: University Hospital Essen, Essen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Dürig
authors.affiliation: Rush University Medical Center, Chicago, IL, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Gregory
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kalaycio
authors.affiliation: Institut Paoli Calmettes, Marseille, France.
authors.forename: T
authors.initials: T
authors.lastname: Aurran-Schleinitz
authors.affiliation: Padua University School of Medicine, Padua, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Trentin
authors.affiliation: Barts Cancer Institute, Queen Mary, University of London, London, UK.
authors.forename: J G
authors.initials: JG
authors.lastname: Gribben
authors.affiliation: Mayo Clinic, Jacksonville, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Chanan-Khan
authors.affiliation: Celgene Corporation, Summit NJ, USA.
authors.forename: B
authors.initials: B
authors.lastname: Purse
authors.affiliation: Celgene Corporation, Summit NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Celgene Corporation, Boudry, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: De Bedout
authors.affiliation: Celgene Corporation, Summit NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department I of Internal Medicine, University of Cologne, Cologne, Germany.|Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD), Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Stilgenbauer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012008:Recurrence; D019233:Retreatment; D016019:Survival Analysis; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D007143:Immunoglobulin Heavy Chains; D007155:Immunologic Factors; D016159:Tumor Suppressor Protein p53; D013792:Thalidomide; D000077269:Lenalidomide