Real-world Outcomes With Cumulative Bortezomib Dose and Efficacy in the Treatment of Transplant-ineligible Multiple Myeloma With Cyclophosphamide, Bortezomib, and Dexamethasone.

Abstract

Higher cumulative dose of bortezomib, a key component of Multiple Myeloma (MM) treatment regimens, has been shown to improve outcomes in MM patients, but must be balanced with toxicities including peripheral neuropathy. In this study, we studied the effect of cumulative bortezomib dose on survival, depth of response, and discontinuation rate in transplant ineligible MM patients. Data from 70 patients treated with Cyclophsophamide, Bortezomib, and Dexamethasone (CyBorD) in a single Canadian center were grouped according to above vs below median cumulative bortezomib dose and analyzed for progression-free survival (PFS), overall survival (OS), depth of response, and discontinuation rate. There was a trend for lower discontinuation rate (45.7% vs. 68.6%, P=.052) and significantly lower rate of neuropathy-related discontinuation (5.7% vs. 22.9%, P=.035) in patients who received higher than 43.1 mg/m² of bortezomib. The higher-dose group showed a trend for higher rate of complete response (14.3% vs. 5.7%, P=.225) and significantly higher rate of very good partial response or better (77.1% vs. 51.4%, P=.024). There was significantly longer PFS (24.3 vs. 9.1 months, P=.012) and a trend for longer OS (22.4 vs. 61.3 months, P=.061) in the higher-dose group. In landmark analysis after 180 days, PFS (23.5 vs. 24.3 months, P=.941) and OS were similar in both groups. Higher cumulative bortezomib dose showed a lower rate of discontinuation, longer survival, and deeper response. Determining risk of treatment intolerance remains important for treatment.