Autores: Dimopoulos, M. A.; Mateos, M. V.; Richardson, P. G.; Schlag, R.; Khuageva, N. K.; Shpilberg, O.; Kropff, M.; Spicka, I.; Palumbo, A.; Wu, K. L.; Esseltine, D. L.; Liu, K.; Deraedt, W.; Cakana, A.; van de Velde, H.;
San Miguel Izquierdo, Jesús
Resumen:
Objectives: This subanalysis of the phase 3 VISTA trial aimed to assess the frequency, characteristics and reversibility of, and prognostic factors for, bortezomib-associated peripheral neuropathy (PN) in newly diagnosed patients with multiple myeloma ineligible for high-dose therapy who received bortezomib plus melphalan-prednisone.
Methods: Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m(2), days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, and days 1, 8, 22, 29, cycles 5-9; melphalan 9 mg/m(2), days 1-4, cycles 1-9; and prednisone 60 mg/m(2), days 1-4, cycles 1-9).
Results: Overall, 47% of patients receiving VMP developed PN, including 19% grade 2 and 13% grade ¿ 3 (<1% grade 4). The PN incidence was dose-related and reached a plateau at a cumulative bortezomib dose of approximately 45 mg/m(2). Median time to PN onset was 2.3 months. Bortezomib-associated PN was reversible; 79% of events improved by at least one NCI CTCAE grade within a median of 1.9 months and 60% completely resolved within a median of 5.7 months, with reversibility similar in responding and non-responding patients. By multivariate analysis, baseline neuropathy was the only consistent risk factor for any PN [hazard ratio (HR) 1.785, P=0.0065], grade ¿ 2 PN (HR 2.205, P=0.0032), and grade ¿ 3 PN (HR 2.438, P=0.023); age, pre-existing diabetes, International Staging System stage, obesity, and creatinine clearance did not affect the overall rate of PN.
Conclusions: Rates of bortezomib-induced PN in the frontline setting were similar to those in relapsed patients and resolved in most cases.
Trial registration: ClinicalTrials.gov NCT00111319.
