title: Safety and efficacy of different lenalidomide starting doses in patients with relapsed or refractory chronic lymphocytic leukemia: results of an international multicenter double-blinded randomized phase II trial.
abstract: The objective of this study was to evaluate the safety and efficacy of different lenalidomide starting doses in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). CLL patients were randomized to receive lenalidomide at initial doses of 5, 10, or 15 mg/d (N = 103). Doses were escalated by 5 mg every 28-d up to a maximum of 25 mg/d; dose reductions in up to 5 mg decrements were permitted. The most common grade ≥3 adverse events (AEs) were neutropenia and thrombocytopenia. Ten patients died during therapy (four deaths considered as related to lenalidomide); 12 patients experienced second primary malignancies. The most common cause for treatment discontinuation was AEs. Overall response rates were similar across arms. Progression-free survival and overall survival rates were longer in patients who escalated treatment (to 15 or 20 mg/d) versus those who did not. Lower starting doses allowed subsequent dose escalation of lenalidomide while maintaining an acceptable tolerability profile in patients with relapsed/refractory CLL.
authors.affiliation: a Klinikum Schwabing, Academic Teaching Hospital of University of Munich , Munich , Germany ;|b Department I of Internal Medicine , University of Cologne , Cologne , Germany ;
authors.forename: Clemens M
authors.initials: CM
authors.lastname: Wendtner
authors.affiliation: b Department I of Internal Medicine , University of Cologne , Cologne , Germany ;|c Cologne Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases (CECAD) , Cologne , Germany ;
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.affiliation: d Juravinski Cancer Centre, McMaster University , Hamilton , Ontario , Canada ;
authors.forename: Graeme A M
authors.initials: GA
authors.lastname: Fraser
authors.affiliation: e Hospices Civils De Lyon, Centre Hospitalier Lyon Sud , Pierre Bénite , Lyon , France ;
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Michallet
authors.affiliation: f St James's Institute of Oncology , Leeds , UK ;
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.affiliation: g University Hospital Essen , Essen , Germany ;
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.affiliation: h Cleveland Clinic , Cleveland , OH , USA ;
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
authors.affiliation: i Barts Cancer Institute, Queen Mary, University of London , London , UK ;
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.affiliation: j Department of Internal Medicine III , Ulm University , Ulm , Germany ;
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: j Department of Internal Medicine III , Ulm University , Ulm , Germany ;
authors.forename: Andreas
authors.initials: A
authors.lastname: Buhler
authors.affiliation: k University of California San Diego Moores Cancer Center , La Jolla , CA , USA ;
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.affiliation: l Celgene Corporation , Summit , NJ , USA ;
authors.forename: Brendan
authors.initials: B
authors.lastname: Purse
authors.affiliation: l Celgene Corporation , Summit , NJ , USA ;
authors.forename: Jennie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: m Celgene Corporation , Boudry , Switzerland ;
authors.forename: Sabine
authors.initials: S
authors.lastname: De Bedout
authors.affiliation: l Celgene Corporation , Summit , NJ , USA ;
authors.forename: Jay
authors.initials: J
authors.lastname: Mei
authors.affiliation: n Mayo Clinic , Jacksonville , FL , USA.
authors.forename: Asher
authors.initials: A
authors.lastname: Chanan-Khan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012008:Recurrence; D019233:Retreatment; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D013792:Thalidomide; D000077269:Lenalidomide
keywords: CLL; Clinical trial; lenalidomide; phase II