Efficacy and Safety of a Weekly Cyclophosphamide-Bortezomib-Dexamethasone Regimen as Induction Therapy Prior to Autologous Stem Cell Transplantation in Japanese Patients with Newly Diagnosed Multiple Myeloma: A Phase 2 Multicenter Trial

• Published in: Acta haematologica Vol. 141; no. 2; p. 111
• Main Authors: Tanaka, Keisuke, Toyota, Shigeo, Akiyama, Megumi, Wakimoto, Naoki, Nakamura, Yuichi, Najima, Yuho, Doki, Noriko, Kakihana, Kazuhiko, Igarashi, Aiko, Kobayashi, Takeshi, Ohashi, Kazuteru, Kudo, Daisuke, Shinagawa, Atsushi, Takano, Hina, Fujio, Takayuki, Okoshi, Yasushi, Hori, Mitsuo, Kumagai, Takashi, Saito, Tatsuya, Mukae, Junichi, Yamamoto, Koh, Tsutsumi, Ikuyo, Komeno, Takuya, Yoshida, Chikashi, Yamamoto, Masahide, Kojima, Hiroshi
• Format: Journal Article
• Language: English
• Published: Switzerland 01.01.2019
• Subjects: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bortezomib - administration & dosage; Bortezomib - adverse effects; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Drug Administration Schedule; Female; Hematologic Diseases - etiology; Hematopoietic Stem Cell Transplantation; Humans; Japan; Male; Middle Aged; Multiple Myeloma - diagnosis; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Young Adult; Japan; Cyclophosphamide; Bortezomib; Dexamethasone; Induction; Multiple myeloma; Weekly cyclophosphamide-bortezomib-dexamethasone; Autologous stem cell transplantation
• ISSN: 1421-9662
• DOI: 10.1159/000495338

We assessed the efficacy and safety of weekly cyclophosphamide-bortezomib-dexamethasone (CBD) induction prior to autologous stem cell transplantation (ASCT) in newly diagnosed Japanese patients with multiple myeloma (MM). This regimen consisted of four 28-day cycles of once-weekly oral cyclophosphamide (300 mg/m2), subcutaneous bortezomib (1.3 mg/m2), and oral dexamethasone (40 mg). Responding patients underwent stem cell collection followed by ASCT. The primary endpoint was the postinduction rate of achieving a near complete response (nCR) or better. Among the 38 enrolled patients, a complete response (CR), an nCR, a very good partial response (VGPR), and a partial response (PR) were achieved in 10.5, 2.6, 23.7, and 36.8% of cases, respectively. A grade 4 hematological adverse event (AE) was observed in 1 patient. Grade 3-4 infection, including febrile neutropenia, was observed in 4 patients (10.5%). Although 2 patients dropped out due to AE, 94.7% of the patients completed the induction phase. However, because of a poor response to induction chemotherapy (<PR in 6 patients), poor stem cell mobilization (4 patients), and a protocol violation (1 patient), only 24 patients (63.2%) proceeded to ASCT. The 2-year progression-free and overall survivals were 55.3 and 82.7%, respectively. We thus believe that the therapeutic power of weekly CBD is not strong enough as a 3-drug induction regimen despite its feasibility for most Japanese patients.