Dose intensity and treatment duration of bortezomib in transplant-ineligible newly diagnosed multiple myeloma

Background Bortezomib-related peripheral neuropathy (PN) affects a relevant proportion of multiple myeloma (MM) patients treated with melphalan, prednisone, and bortezomib (VMP). Empirical dose modifications have attempted to reduce toxicity without compromising efficacy. Patients and methods We retrospectively evaluated the dose-response and dose-toxicity relationships in 114 unselected untreated MM patients intended for treatment with VMP with subcutaneous bortezomib. Results Sixty-two patients (54%) completed the 9 scheduled cycles. Median treatment duration was 48 weeks (range 1-57), cumulative bortezomib dose was 41.8 mg/m(2) (2.6-67.6) and median dose intensity was 1.0 mg/m(2)/wk (0.2-2.6). Median progression-free survival (PFS) and overall survival (OS) for the full cohort were 86 weeks (95%CI 77-104) and 209 weeks (95% CI 157-259) respectively. Patients who progressed <60 days after discontinuing bortezomib had received a significantly inferior mean cumulative dose, 34.6 mg/m(2) than the remaining individuals, 45.5 (P = .023). PFS was significantly improved for patients achieving a very good partial response (VGPR) or better (P = .00007). Additional variables with a prognostic impact on PFS on univariate analysis included completion of the 9 scheduled cycles (P = .00002), patients with at least 50 weeks of treatment (P = .02) and patients receiving a cumulative dose of at least 49 mg/m(2) (P = .05). Achievement of a VGPR (HR 0.23; 95%CI 0.12-0.46; P = .00002) and a cumulative dose of 49 mg/m(2) (HR 0.46, 95%CI 0.27-0.78; P = .003) were statistically independent prognostic factors for PFS. Toxicity-related treatment dose reductions occurred in 75 individuals (66%). PN was observed in 50 individuals (44.6%), grade 3 in 9 (8%). The only prognostic factor for emergence of PN in multivariate analysis was the presence of baseline PN. Conclusions Biweekly full-dose treatment in the first cycles has a major impact in depth of response. Depth of response, cumulative bortezomib dose, and treatment duration had an impact in prolongation of PFS.