title: Elotuzumab with lenalidomide and dexamethasone for Japanese patients with relapsed/refractory multiple myeloma: phase 1 study.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. iida@med.nagoya-cu.ac.jp.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Bristol-Myers Squibb K.K., Tokyo, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Kinoshita
authors.affiliation: Bristol-Myers Squibb K.K., Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Miyoshi
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Robbins
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Dimple
authors.initials: D
authors.lastname: Pandya
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Bleickardt
authors.affiliation: Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Chou
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage; D004359:Drug Therapy, Combination / Q000379:methods* / Q000592:standards; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D007970:Leukopenia / Q000139:chemically induced; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D012008:Recurrence; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000378:metabolism; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C448987:SLAMF7 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; C546027:elotuzumab; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide
keywords: Elotuzumab; Phase 1; Relapsed/refractory multiple myeloma