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 relatively new drug in the treatment of patients with Multiple Myeloma (MM). Most data on efficacy and safety are from randomised controlled studies in selected groups of patients with MM. Aim of the study: To evaluate safety and efficacy of bortezomib in daily practice after its registration for second and later line therapy in patients with MM. Materials and methods: In an observational, multicentre study, the efficacy and safety of treatment with bortezomib was assessed in MM patients. An interim analysis was performed on data of the first 50 patients enrolled from November 04 until March 06. Results: All results are given as median ± SD. The patients’ age was 65 yrs, Karnofsky Performance Score was 80%, time from initial diagnosis was 3.4 years, 62% of the patients had more than 2 previous treatment lines, 88% of the patients had disease stage III. Patients were treated with 4 cycles (95% CI: 4.0 – 5.4) of bortezomib. The patients had Response Rate (RR; based on serum M-protein values) of 64% (2.0% nCR, 2.0% VGPR, 22% PR, 38% MR). Best RR remained 64% with an increasing depth of response (2% CR, 8% nCR 6.0% VGPR, 32% PR, 16% MR); 6 patients were not evaluable for response. Time to initial response was 45 days; time to best response was 63 days. The duration of response (DOR) was 6.4 months. Also, a relation between treatment duration and DOR was found (correlation coefficient 0.4118, p-value 0.0192). Overall survival was 1.3 yrs and PFS 6.4 months. The treatment was generally well tolerated. Most common adverse events (AE’s) were in order of decreasing frequency thrombocytopenia, nausea, constipation, diarrhoea, fatigue, malaise, polyneuropathy, pyrexia, anaemia, dizziness and leukopenia. Only 6.1% of all AE’s resulted in a permanent discontinuation of bortezomib; 13% of all AE’s were reported as serious of which 54.7% were considered as grade 3 or higher (CTCAE) and at least possibly related to bortezomib in 45.3%. In one patient (2%), Herpes zoster was reported. Conclusion: Response Rates in this study were comparable to those in other community studies and higher than reported in previous clinical studies. The somewhat shorter DOR observed versus previously reported studies might have been caused by a shorter duration of bortezomib treatment, although more data is needed to derive a final conclusion. Overall the treatment with bortezomib was well tolerated and overall survival was as expected in this patient population. The clinical significance of the observed relation between treatment duration and response duration requires further exploration.