Efficacy and Safety of Once-Weekly Bortezomib Infusion in the Treatment of Relapsed/Refractory Multiple Myeloma

Abstract 5141

Incorporation of bortezomib in the treatment of multiple myeloma (MM) has significantly imporved patient outcome. Because peripheral neuropathy (PN) leading to dose modification and drug discontinuation seems to be dependent on dose and exposure of bortezomib, some schedules of botezomib therapy were reduced from twice-weekly to once-weekly infusion. We assessed the efficacy and safety of once-weekly bortezomib infusion in the treatment of relapsed/refractory MM.

We compared the outcomes and safety of once- and twice-weekly bortezomib infusion as a second-line treatment for the patients of relapsed/refractory MM in our hospital between 2005 and 2010, retrospectively.

Twenty-nine patients were enrolled including 12 patients who received once-weekly bortezomib infusion on day 1, 8, 15 and 22 of the cycles and 19 patients who received twice-weekly bortezomib infusion on day 1, 4, 8 and 11 of the cycles as a second-line treatment. Dexamethasone alone (n=18), melpahalan with prednisolone (n=4), and thalidomide with dexamethasone (n=7) were administered combined with bortezomib. Median cumulative dose of bortezomib were 32.4mg/m² and 18.4mg/m² in the once- and twice-weekly group, retrospectively (p=0.019). There were no significant difference in overall response rate (66.7% in once-weekly vs 47.1% in twice-weekly, p=0.451) and time-to-progression (median 17.2 months in once-weekly vs 7.1 months in twice-weekly, p=0.381). There was a significant difference in the median time-to-onset of grade 2 to 4 PN (4.5 months in once-weekly vs 2.0 months in twice-weekly, p=0.017). The incidence of grade 2–4 PN (50.0% vs 47.1%) and median cumulative dose to onset of grade 2–4 PN (17.9mg/m² vs 15.3mg/m²) were not different. The incidence of any grade 3/4 toxicity except PN was similar (25.0% vs 41.2%, p=0.449). Progression-free survival in once-weekly bortezomib group was slightly longer than that in twice-weekly bortezomib (median 34.8 months vs median 22.8 months, p=0.074). Overall survival was similar (median 35.2 months vs median 25.1 months, p=0.118), while the overall survival of elderly patients (60 years or above) in once-weekly bortezomib group was slightly longer than that in twice-weekly bortezomib group by Kaplan-Meier analysis (median 38.1 months vs median 20.1 months, p=0.085).

Our data suggest that the onset time of PN was delayed in once-weekly regimen and there was no significant difference overall response, rate of PN, cumulative dose to onset of PN, grade 3/4 toxicity and overall survival between both groups. Because of the larger cumulative dose and the lower rate of dose modification or drug discontinuation due to good tolerability in once-weekly bortezomib than twice-weekly bortezomib, once-weekly bortezomib infusion could be a potential therapeutic approach for patient with MM as a scond-line therapy.