Bortezomib (Velcade ^™) Observational Study in China: Efficacy and Safety of Bortezomib-Based Regimen in 395 Relapsed or Refractory Multiple Myeloma Patients

Introduction: Multiple myeloma (MM) is a plasma-cell malignancy and overall survival for patients who have relapsed after initial therapy is approximately 2 years. Bortezomib (VELCADE TM) is a first-in-class proteasome inhibitor that has demonstrated significant anti-tumor activity in MM patients. Here we report the results of an observational study of the efficacy and safety of bortezomib-based regimens in Chinese relapsed/refractory MM patients.

Methods: This was a multi-center, open-label, phase IV observational study designed to enroll 550 patients with relapsed or refractory MM. From Mar 2006 to May 2008, 500 patients with relapsed or refractory MM were enrolled from 43 medical centers in China and 395 of them were evaluated. Bortezomib (0.7 to 1.6 mg/m2 i.v.) was given on days 1, 4, 8, and 11 in in a 21-day cycle, up to a maximum of 8 cycles, combined with other agents, mainly with the addition of dexamethasone (60.1%). Major endpoint included response rate, safety and time to response. Responses of 62% patients were determined by European Group for Blood and Marrow Transplantation criteria (EBMT). Bortezomib withheld if patients developed neutropenia fever, grade 4 haematologic adverse events (AEs), or grade 3 non-haematologic AEs, and re-administered at 75% of the initial dosage after recovery.

Results: In 395 evaluable cases, the median age was 59 years (range 35–82) and the male/female ratio was 1.5:1. 90% of patients were in late stage(stage II/III) and 50% of them were IgG subtype. Patients had received various prior therapies before bortezomib treatment, including VAD (31.3%), VBMCP (M2, 15.1%) and thalidomide-based regimens(14.9%), with best response rate of 10.4% complete response (CR) and 42.3% partial response (PR) from prior therapies. 311 (82%) cases of patients received 1.0–1.4mg/m2 bortezomib-based regimens treatment and 38.5% of them received at least 4 cycles of treatment. 364 patients were evaluable for response, the overall response rate was 287/364 (78.8%), 89 patients (24.5%) achieved a CR, 30(8.24%) had a nearly complete response (nCR), 168 (46.2%) had a PR, 39 (10.7%) had minimal response (MR), 24 (6.6%) had stable disease (SD), and the other 14 (3.9%) had progressive disease (PD). Median time to response was 1 cycle of treatment (range 1–6). Patients who received 4 or more cycles of bortezomib treatment achieved a higher response rate (CR+PR: 81.5%) compared to those who received fewer cycles (partly due to adverse events). And prognosis-related analysis showed that the dosage of bortezomib at 1.0 mg/m2 or more had a significant influence on the time to response and response rate, but no obvious effect on response duration, time to progress or the survival time. Drug related adverse events (AEs) were reported in 50.4% of patients during treatment, including hematologic AEs (mainly thrombocytopenia, 22.5%), gastrointestinal AEs (24.8%), and peripheral neuropathy (22.5%). The rates of grade 3–4 AEs of them were 46.1%, 11.2% and 15.7%, respectively. Serious AEs occurred in 33 (8.4%) cases and 23 (70%) patients recovered finally. Most AEs were predictable and manageable.

Conclusion: Bortezomib-based regimen is effective treatment with higher response rate and is well tolerated in most Chinese patients with relapsed and refractory MM patients. Long-term follow-up is continuing.