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.

Abstract

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.

• Authors: Keisuke Tanaka, Shigeo Toyota, Megumi Akiyama, Naoki Wakimoto, Yuichi Nakamura, Yuho Najima, Noriko Doki, Kazuhiko Kakihana, Aiko Igarashi, Takeshi Kobayashi, Kazuteru Ohashi, Daisuke Kudo, Atsushi Shinagawa, Hina Takano, Takayuki Fujio, Yasushi Okoshi, Mitsuo Hori, Takashi Kumagai, Tatsuya Saito, Junichi Mukae, Koh Yamamoto, Ikuyo Tsutsumi, Takuya Komeno, Chikashi Yoshida, Masahide Yamamoto, Hiroshi Kojima, on behalf of the Ochanomizu Hematology Study Group
• Journal: Acta haematologica (Acta Haematol) Vol. 141 Issue 2 Pg. 111-118 ( 2019) ISSN: 1421-9662 [Electronic] Switzerland
• PMID: 30726834 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2019 S. Karger AG, Basel.

Chemical References

• Bortezomib
• Dexamethasone
• Cyclophosphamide

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bortezomib (administration & dosage, adverse effects)
• Cyclophosphamide (administration & dosage, adverse effects)
• Dexamethasone (administration & dosage, adverse effects)
• Drug Administration Schedule
• Female
• Hematologic Diseases (etiology)
• Hematopoietic Stem Cell Transplantation
• Humans
• Japan
• Male
• Middle Aged
• Multiple Myeloma (diagnosis, drug therapy, mortality)
• Survival Analysis
• Transplantation, Autologous
• Treatment Outcome
• Young Adult