Elotuzumab with lenalidomide and dexamethasone for Japanese patients with relapsed/refractory multiple myeloma: phase 1 study

• Published in: International journal of hematology Vol. 105; no. 3; pp. 326 - 334
• Main Authors: Iida, Shinsuke, Nagai, Hirokazu, Kinoshita, Gen, Miyoshi, Masafumi, Robbins, Michael, Pandya, Dimple, Bleickardt, Eric, Chou, Takaaki
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.03.2017; Springer Nature B.V
• Subjects: Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Dexamethasone; Dexamethasone - administration & dosage; Drug Therapy, Combination - methods; Drug Therapy, Combination - standards; Female; Hematology; Humans; Immunostimulation; Immunotherapy; Killer cells; Lenalidomide; Leukopenia; Leukopenia - chemically induced; Lymphopenia; Lymphopenia - chemically induced; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Multiple myeloma; Multiple Myeloma - complications; Multiple Myeloma - drug therapy; Natural killer cells; Oncology; Original Article; Patients; Pharmacokinetics; Recurrence; Safety; Salvage Therapy - adverse effects; Salvage Therapy - methods; Signaling Lymphocytic Activation Molecule Family - metabolism; Steroids; Targeted cancer therapy; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives; Toxicity; Treatment Outcome; Relapsed/refractory multiple myeloma; Elotuzumab; Phase 1
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-016-2138-4

Elotuzumab is an immunostimulatory monoclonal antibody that binds to SLAMF7, a type-1 transmembrane protein expressed on myeloma and natural killer cells. We report a phase 1 study (NCT01241292) in which we evaluated the safety, efficacy and pharmacokinetics of elotuzumab combined with lenalidomide and dexamethasone in Japanese patients with relapsed/refractory multiple myeloma (RRMM). In 28-day cycles, patients received: elotuzumab (intravenously), lenalidomide (25 mg orally) and weekly dexamethasone (elotuzumab days: 28 mg orally plus 8 mg intravenously; non-elotuzumab days: 40 mg orally). Elotuzumab dose was initially 10 mg/kg (Cohort 1, n  = 3) and, if no dose-limiting toxicities (DLTs) occurred, increased to 20 mg/kg (Cohort 2, n  = 3). No DLTs occurred in the six patients treated. Maximum (median) durations of study therapy were 36.6 (35.2) months in Cohort 1 and 28.3 (9.2) months in Cohort 2. Leukopenia and lymphopenia were observed in all patients. No adverse events led to treatment discontinuation. Overall response was 83% ( n  = 5): one complete response, three very good partial responses, one partial response. Three patients are still undergoing treatment, with responses maintained. Expression of SLAMF7 was immunohistochemically detected in all patients. We find that elotuzumab combined with lenalidomide and dexamethasone exhibited acceptable safety/tolerability in Japanese patients with RRMM, with durable efficacy.