title: Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan.
abstract: This is the first study in which the carfilzomib, lenalidomide and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open-label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM) patients. The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics of the regimen. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m2, followed by 27 mg/m2. Lenalidomide and dexamethasone were administered at 25 mg (days 1-21) and 40 mg (days 1, 8, 15 and 22), respectively. Twenty-six patients were enrolled. Patients had received a median of four prior regimens and 88.5% and 61.5% received previous bortezomib and lenalidomide, respectively. High-risk cytogenetics were seen in 53.8% of patients. The overall response rate was 88.5%. A higher rate of hyperglycemia was observed than in a previous carfilzomib monotherapy study, but this was attributed to dexamethasone. Carfilzomib pharmacokinetics were not affected by lenalidomide and dexamethasone. The KRd regimen was well tolerated and showed efficacy in Japanese RRMM patients.
authors.affiliation: Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Kenshi
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ri
authors.affiliation: Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Chou
authors.affiliation: Division of Hematology and Oncology, Toyohashi Municipal Hospital, Toyohashi.
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugiura
authors.affiliation: Department of Hematology, National Hospital Organization Disaster Medical Center, Tachikawa, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takezako
authors.affiliation: Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Sunami
authors.affiliation: Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.|Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Hematology, Tochigi Cancer Center, Utsunomiya, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
authors.affiliation: Department of Hematology, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ozaki
authors.affiliation: Department of Oncology Clinical Development Planning, Ono Pharmaceutical, Osaka, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Shumiya
authors.affiliation: Department of Oncology Clinical Development Planning, Ono Pharmaceutical, Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ota
authors.affiliation: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007564:Japan; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009842:Oligopeptides / Q000627:therapeutic use*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D013792:Thalidomide; C524865:carfilzomib; D003907:Dexamethasone; D000077269:Lenalidomide
keywords: Japan; carfilzomib; dexamethasone; lenalidomide; multiple myeloma