title: Dose-escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma.
abstract: B-cell activating factor (BAFF) promotes the survival and adhesion of multiple myeloma (MM) cells. Tabalumab (LY2127399) is an anti-BAFF monoclonal antibody. This phase 1, multicenter, open-label, nonrandomized, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of tabalumab in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory MM (RRMM). Sixteen patients received intravenous i.v. tabalumab 100 mg (Cohort 1, n = 4) or i.v. tabalumab 300 mg (Cohort 2, n = 12) in combination with oral dexamethasone 20 mg/day and i.v. or s.c. bortezomib 1.3 mg/m(2) . All patients had treatment-emergent adverse events (TEAE) possibly related to study treatment; the most common TEAE were thrombocytopenia (81.3%), lymphopenia (43.8%) and increased alanine aminotransferase (43.8%). Two (20.0%) dose-limiting toxicities were observed, both in Cohort 2 (tabalumab 300 mg), which was below the predefined cutoff for tolerability (<33%). The pharmacokinetics of tabalumab were similar when bortezomib was coadministered i.v. versus s.c. The overall response rate was 56.3%, suggesting that the combined treatment was effective. In conclusion, combined treatment with these three agents was well tolerated in this population of Japanese patients with RRMM. The study was registered at www.clinicaltrials.gov (NCT01556438).
authors.affiliation: Department of Hematology and Oncology, Nagoya City University Hospital, Nagoya, Japan. iida@med.nagoya-cu.ac.jp.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ogiya
authors.affiliation: Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.affiliation: Medical Science, Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Asou
authors.affiliation: Medical Science, Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: Kaijiro
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Japan PK/PD, Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Uenaka
authors.affiliation: Statistical Science, Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: Soshi
authors.initials: S
authors.lastname: Nagaoka
authors.affiliation: Science Communications, Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishiki
authors.affiliation: Global Medical, Eli Lilly and Company, Indianapolis, Indiana, USA.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Conti
authors.affiliation: Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage / Q000493:pharmacokinetics; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D018450:Disease Progression; D016903:Drug Monitoring; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069286:Bortezomib; D003907:Dexamethasone; C575974:tabalumab
keywords: Anti-B-cell activating factor monoclonal antibody; LY2127399; multiple myeloma; phase 1 study; tabalumab