Bortezomib (Velcade™) Observational Study in China - Efficacy and Safety of Bortezomib Based Regimen in 223 Relapsed or Refractory Multiple Myeloma Patients.

Introduction: Multiple myeloma (MM) is a plasma-cell malignancy with approximately three years’ median survival. Patients usually relapse or become refractory to existing treatments. Clinical studies have confirmed that bortezomib is an effective agent for relapsed MM patients and has potent synergy with other chemotherapeutic agents, which provides a new clinical regimen that may improve response. In this observational study, we intend to observe the safety/tolerability and efficacy of bortezomib-based regimens in Chinese patients with relapsed/refractory MM.

Methods: This was a multicenter, open-label, phase IV observational study for patients with relapsed or refractory MM. Bortezomib (0.7 to 1.6 mg/m² i.v.) was given on days 1, 4, 8, and 11 of a 21-day cycle, for a maximum of 8 cycles, combined with other agents, mainly of dexamethasone addition. If pyretic neutropenia, grade 4 hematologic adverse events (AEs), or grade ≥3 non-hematologic AEs developed, bortezomib treatment was temporarily discontinued and re-administered at 75% of the initial dosage after remittance of the AEs. Responses were classified mainly by European Group for Blood and Marrow Transplantation criteria (EBMT).

Results: Between Mar 2006 and May 2007, 223 patients with MM were enrolled at 31 medical centers. Median age was 58 years (range 35–82), 96% of patients were in stage II/III, and the most common subtype was IgG (46%). Patients had received various prior therapies such as VAD (29% of patients), VBMCP (M2) (16%), and thalidomide combinations (15%). There were 198 patients evaluable for response, of whom 54 (27%) achieved a complete response (CR), 99 (50%) achieved a partial response (PR), 20 (10%) had minimal response (MR), 16 (8%) had stable disease (SD), and the other 9 (5%) had progressive disease (PD). Patients who received 4 or more cycles of bortezomib achieved a higher CR rate (56%) compared with patients who received fewer cycles (partly due to adverse event). Rapid responses were seen with the median time to response being 1 cycle (range 1–5). Common predictive factors including age, isotype, number of previous therapies, concentration of C-reactive protein, or beta2-microglobulin had no significant influence on treatment response. The incidence of adverse events (AEs) was 54%, including 18% of patients with hematologic AEs (33% of them grade 3–4), 27% with gastrointestinal AEs (50% of them grade 3–4), and 20% with peripheral neuropathy (40% of them grade 3–4). Serious AEs occurred in 25 (11%) patients. Most AEs were predictable and manageable.

Conclusions: These data demonstrate that a bortezomib-based regimen is a promising regimen with high response rate and is well tolerated in most relapsed and refractory MM patients. Additional clinical trials and long-term follow-up on Chinese patients are warranted.