International Observational Study On Bortezomib (VELCADE) in Relapsed Multiple Myeloma: Preliminary Efficacy and Quality of Life (QoL) Results From the Belgian Population.

Bortezomib (VELCADE) is a proteasome inhibitor for treatment of MM. The eVOBS (electronic VELCADE Observational Study) evaluates treatment and clinical outcome with bortezomib in daily practice in the relapsed setting. Enrollment in the study started in Oct 06 and is still continuing, with 3 y follow-up for every enrolled patient. This report concerns preliminary efficacy and Quality of Life (QoL) results of 136 Belgian patients included in the latest interim analysis from June 2009.

Adults were eligible for study if they were scheduled to initiate bortezomib within the approved indication. All bortezomib dosages and concomitant treatments were permitted, except investigational therapies. Due to the non-interventional nature of the study, no predefined response criteria were mandated; response criteria included M-protein, EBMT, SWOG, or others as defined by the investigator. QoL assessment was conducted in Belgium only, using the EORTC Quality of Life Core Questionnaire (QLQ-C30). The EORTC QLQ-C30 comprises a global health status (GHS) scale, five functional scales and six symptom scales. The questionnaire was administered at baseline and at the start of each treatment cycle. Evolution of mean scores was determined in correlation with baseline characteristics and response. Results were also analyzed for all patients and responders (partial response (PR) or better) vs. non-responders. For this, a mixed model was used comparable to that described by Lee et al. [BJH (2008) 143, 511-519], with missing data due to death being assigned the lowest possible score (model A) vs. being treated as missing (model B). Predictive value of baseline QoL scores for Overall Survival (OS) and Progression Free Survival (PFS) was assessed.

One hundred thirty six patients (57% male) are included in this analysis, with median age of 65y, and mean time since MM diagnosis of 2.9 years. Prior number of therapies received was 1 in 56%, 2 in 27%, and 3 or more in 11%. Five % received bortezomib in first line and for 1% data were missing. 97% of patients started bortezomib at 1.3 mg/m² on the standard schedule. Median treatment duration was 5 cycles. Of the 97 patients that were evaluated for response so far, overall response rate was 69%, with 57% PR and 12% CR/nCR. 14% and 9% of patients reached MR and SD, respectively. 78% of all enrolled patients experienced AEs of any grade, which led to discontinuation of treatment in 30%, comparable with the 37% in the APEX trial (Richardson, NEJM 2005). For QOL assessment 103 patients completed the EORTC QLQ C-30 at baseline, with this number decreasing substantially in subsequent cycles (n=42 by cycle 4). Using model A (death = worst possible outcome), a small but significant decline in QoL was seen for physical, role, emotional, cognitive and social functioning, and for symptom scales of nausea and vomiting and financial impact. Of these, only the decline in cognitive functioning remained significant when applying model B (death = missing). In the APEX trial as well there was a decline in GHS as well as in 8 of the EORTC scale scores (Lee et al BJH 2008). No significant differences were seen according to baseline data (gender, age, line of therapy, lab values). Using model A, the evolution of QoL scores was significantly worse for non-responders vs. responders on the scales of physical, cognitive and emotional functioning, nausea and vomiting, sleep disturbance, diarrhea and financial impact. When using model B, no significant differences in QOL between responder and non-responder groups were detected. Worse baseline scores for nausea and vomiting and dyspnoea were predictive for worse PFS, but only dyspnoea was predictive for worse OS.

Overall in this study a slight decline was seen for some QoL parameters over the course of treatment, consistent with findings from the APEX trial (Lee et al. BJH 2008), which included patients similar to those in the eVOBS trial (Zervas IMW 2009). Using the model that assigns “worst possible outcomes” to data missing because of death, better QoL was seen in responders vs. non-responders, suggesting better QoL is at least partly linked to response. Interpretation should be done with caution due to the number of patients and the decreasing number of returned questionnaires over time.

Delforge:Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Van Droogenbroeck:Celgene: Consultancy; BMS: Consultancy; Novartis: Consultancy; Janssen-Cilag: Consultancy. Kuijten-Celzo:Johnson & Johnson: Employment. Diels:Johnson & Johnson: Employment. Ganguly:Johnson & Johnson: Employment, Equity Ownership. Dhawan:Johnson and Johnson Research Pharmaceuticals: Employment.