Elotuzumab in Combination With Lenalidomide and Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma

• Published in: Journal of clinical oncology Vol. 30; no. 16; pp. 1953 - 1959
• Main Authors: LONIAL, Sagar, VIJ, Ravi, SINGHAL, Anil K, JAGANNATH, Sundar, HAROUSSEAU, Jean-Luc, FACON, Thierry, MOREAU, Philippe, MAZUMDER, Amitabha, KAUFMAN, Jonathan L, LELEU, Xavier, CLAIRE TSAO, L, WESTLAND, Christopher
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.06.2012
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Dexamethasone - administration & dosage; Disease Progression; Drug Administration Schedule; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Medical sciences; Middle Aged; Multiple Myeloma - drug therapy; Recurrence; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives; Tumors; Antineoplastic agent; Corticosteroid; Immunopathology; Drug combination; Relapse; Treatment resistance; Dexamethasone; Lenalidomide; Steroid hormone; Low dose; Malignant hemopathy; Monoclonal antibody; Myeloma; Cancerology; Immunoglobulinopathy; Lymphoproliferative syndrome; Elotuzumab; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2011.37.2649

This phase I study evaluated elotuzumab, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma (MM). Three cohorts were enrolled and treated with elotuzumab (5.0, 10, or 20 mg/kg intravenously) on days 1, 8, 15, and 22 of a 28-day cycle in the first two cycles, and days 1 and 15 of each subsequent cycle; lenalidomide 25 mg orally [PO] on days 1 to 21; and dexamethasone 40 mg PO weekly. Dose-limiting toxicities (DLTs) were assessed during cycle 1 of each cohort, and clinical responses were evaluated during each cycle. The first five patients received up to six cycles of therapy; subsequent patients were treated until disease progression. Twenty-nine patients with advanced MM and a median of three prior MM therapies were enrolled; 28 patients were treated, three each in the 5.0-mg/kg and 10-mg/kg cohorts and 22 in the 20-mg/kg cohort. No DLTs were observed up to the maximum proposed dose of 20 mg/kg. The most frequent grade 3 to 4 toxicities were neutropenia (36%) and thrombocytopenia (21%). Two patients experienced a serious infusion reaction (one grade 4 anaphylactic reaction and one grade 3 stridor) during the first treatment cycle. Objective responses were obtained in 82% (23 of 28) of treated patients. After a median of 16.4 months follow-up, the median time to progression was not reached for patients in the 20-mg/kg cohort who were treated until disease progression. The combination of elotuzumab, lenalidomide, and low-dose dexamethasone was generally well tolerated and showed encouraging response rates in patients with relapsed or refractory MM.