Bortezomib [VELCADE™], Pegylated Liposomal Doxorubicin [DOXIL/CAELYX®] and Dexamethasone in the Treatment of Previously Untreated Multiple Myeloma Patients: Impact on Quality-of-Life.

Introduction: Bortezomib in combination with liposomal doxorubicin has shown convincing activity as induction therapy in frontline multiple myeloma (MM) patients with CR rates exceeding those seen with conventional induction therapy. The impact of this treatment on patient Quality-of-Life (QOL), determined by overall health status, cancer and neurotoxicity specific questionnaires, is of clinical interest.

Methods: Newly diagnosed Autologous Stem Cell Transplant (ASCT) eligible MM patients were recruited from nine centres across Canada to this single-arm, open-label, Phase II study. Patients received three to four 21-day cycles of DBd induction therapy (bortezomib 1.3mg/m² days 1, 4, 8, 11 + pegylated liposomal doxorubicin 30 mg/m² day 4 + pulsed dexamethasone 40mg days 1–4, 8–11, 15–18 Cycle 1 and days 1–4 cycles 2–4), depending on rapidity of CR achieved, and were then followed post ASCT. Patients completed the European Quality of Life Questionnaire (EQ-5D), the European Organization for Research and Treatment of Cancer’s 30-item Quality of Life Questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire (FACT/GOG-Ntx) prior to each cycle and at study termination.

Results: Fifty patients were enrolled to fulfill the sample size requirement. Mean age was 56.0 (±8.7) years, and 68% of patients were male. Sixty-five percent of the patients had Stage III disease and all but two patients had secretory disease. Mean baseline β₂-microglobulin level was 4.2 (1.5–25.4) mg/mL. Overall best response post-induction was 98% (≥ Minimal Response), with a corresponding 26.8% combined complete response (CR) + near CR rate. There was no significant change in the total EQ-5D score throughout the study when compared to baseline. There was a significant improvement at end of study in the mean EQ-5D VAS self-rated health status (Δ+5.14, p<0.05) compared to baseline. Although not significant, there was a trend towards an increase in the proportion of patients reporting no problem in the mobility and anxiety/depression EQ-5D dimensions over the course of induction therapy. There were also no significant changes observed in the EORTC QLQ-C30 scores. Throughout the study, the FACT/GOG-Ntx scores showed no statistically significant changes over time from baseline, in agreement with the overall clinical safety profile observed. The largest mean score change from baseline was at the end-of-study time point (Δ+1.79, SD±6.07, p=0.06).

Conclusion: Although this study was not powered to detect changes in QOL, preliminary results indicate that there is a trend towards improvement in QOL outcomes in multiple myeloma patients being treated with the DBd induction regimen. These results corroborate the safety and tolerability profile observed in the study.