Effect of the combination of pegylated liposomal doxorubicin and bortezomib on time to progression (TTP) and overall survival of patients with relapsed/refractory multiple myeloma compared with bortezomib alone

Abstract

8002 Background: Proteasome inhibition with bortezomib is a standard of care for patients with relapsed/refractory multiple myeloma (MM). Recently, we reported the results of an interim analysis for the DOXIL-MMY-3001 study, a large multi-national, phase III, randomized study of patients with previously treated MM demonstrating that the combination of pegylated liposomal doxorubicin (PLD) and bortezomib resulted in a 45% risk reduction of experiencing disease progression over bortezomib alone (Orlowski et al, 2006 ASH Meeting, Abstract #404). The improvement in TTP was associated with an overall survival (OS) trend favoring the combination therapy (P=0.113; hazard ratio[HR], 1.48, 95% Confidence Interval [CI], 0.91 to 2.41). We now present an updated survival analysis with a median follow up of 11 months. Methods: 646 patients at 123 centers in 18 countries received either intravenous bortezomib, 1.3 mg/m2, on days 1, 4, 8, and 11 of every 21-day cycle, or the same bortezomib regimen with PLD, 30 mg/m2, on day 4. Results: As previously reported, median TTP was improved from 6.5 months for bortezomib alone to 9.3 months for the PLD+bortezomib combination (P=0.000004; HR, 1.82; 95% CI, 1.41 to 2.35). The complete+partial response rate was 43% for bortezomib and 48% for PLD+bortezomib (P=0.251). Median duration of response was increased from 7.0 months (95% CI, 5.9 to 8.3) to 10.2 months (95% CI, 10.2 to 12.9) with combination therapy (p=0.0008). Updated OS analysis showed PLD+bortezomib significantly improved OS (p<0.05; HR, 1.41, 95% CI, 1.002 to1.97). Both groups received a median of 5 cycles of treatment. The safety profile of the combination was consistent with the known toxicities of the two agents. Grade 3/4 adverse events were more frequent in the combination group primarily due to increase in myelosuppression and GI toxicities. Conclusions: PLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed/refractory MM. [Table: see text]