An Observational Post Authorization Study on the Use of Bortezomib in Multiple Myeloma Patients in the Netherlands: Results of An Interim Analysis

Introduction: Bortezomib (Velcade) is a first-in-class proteasome inhibitor for the treatment of patients (pts) with multiple myeloma (MM). Most data on efficacy and safety are from randomised controlled studies in selected groups of pts with MM.

Aim of the study: To evaluate safety and efficacy of bortezomib in the real-life community oncology practice setting as a second-line therapy or in subsequent lines of therapy in pts with MM.

Materials and methods: In an observational, multicentre study, the efficacy and safety of treatment with bortezomib was assessed in MM pts. An interim analysis was performed on data of pts enrolled from November 04 until November 06 (109 pts).

Results: All results are given as median. The pts age was 67 yrs, Karnofsky Performance Score was 80%, time from initial diagnosis was 3.3 years, 62% of the pts had more than 2 previous lines of treatment, 85% of the pts had disease stage III. Pts were treated with median 4 cycles (95% CI: 4.1–5.0) of bortezomib. Median time to initial response was 50 days and median time to best response category was 84 days. Of all pts 43.2% achieved a partial response or better (2.8% CR, 6.4% nCR, 3.7% VGPR, 30.3% PR); 16 pts were not evaluable for response. The duration of response (DOR) was 6.3 months, PFS was 5.8 months and overall survival was 1.2 yrs. The treatment was generally well tolerated. Most common adverse events (all grades) in >15% of the pts were, in order of decreasing frequency, thrombocytopenia, nausea, diarrhoea, fatigue, (poly)neuropathy, constipation, malaise, anaemia, pyrexia, vomiting and anorexia. For responding pts treatment discontinuation due to an AE occurred in 46.8% of the pts. For the three most common AE’s (polyneuropathy, fatigue/malaise, thrombocytopenia), resulting in discontinuation of the bortezomib treatment, the discontinuation was not preceded by a dose adjustment in almost half of the cases. In 9 pts (8.3%), Herpes zoster reactivation was reported. Twenty-two out of 109 pts were thalidomide naïve when starting bortezomib. 59.4% of these pts achieved a PR or better vs. 39% in thalidomide pre-treated pts, but thalidomide pre-treated pts had a longer time from initial diagnosis (3.5 vs 2.6 years) and had more previous treatment lines compared to thalidomide naïve pts (³ 2 lines of previous therapy 97.7% vs 59.1% respectively).

Conclusion: Response rates in this study were comparable to those in other community studies and higher than reported in previous clinical studies. Overall the treatment with bortezomib was well tolerated. However, it seems dose adjustment as a strategy to continue treatment and to increase the quality of response, is still underutilized in clinical practice. Overall survival was as expected in this patient population. The thalidomide naïve group was yet too small to draw any conclusions on safety and efficacy as compared to the thalidomide pre-treated pts.