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.

The Evaluation of Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients

“…Treatment response rates in both groups were similar to those reported in studies in which the original bortezomib molecule was combined with cyclophosphamide and dexamethasone. In those studies, the rate of any response (PR and above) was 80%, and similar data were obtained in both groups in our study [ 17 , 19 , 20 , 21 ]. The results showed us that the responses of patients using the generic bortezomib molecule were similar to those of patients using the original molecule (81% with the original molecule, 79.2% with the generic).…”

Weekly Cyclophosphamide-Bortezomib-Dexamethasone Induction Performs Comparably to Twice-Weekly Dosing with Respect to Both Response Rates and Survival after Autologous Transplant

“…We conclude that, within the limitations of our retrospective study design, weekly CBD induction performs comparably to twice-weekly dosing with respect to both response rates and survival. As reported by Tanaka et al [1], we see a trend towards lower VGPR or better rate with weekly CBD, but this does not appear to affect outcomes after ASCT. This is consistent with other published “real-world” studies employing weekly bortezomib at the 1.3 mg/m 2 dose [5].…”

“…We read with interest the study by Tanaka et al [1] prospectively evaluating the efficacy and safety of weekly cyclophosphamide-bortezomib-dexamethasone (CBD) induction in transplant-eligible patients with newly diagnosed multiple myeloma. Response rates by intention-to-treat were lower than previously reported, and whilst this may have been attributable to cyclophosphamide dose, the authors conclude that weekly CBD may be less effective than twice-weekly approaches.…”