Risk factors for,and reversibility of,peripheral neuropathy associated with bortezomib–melphalan–prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study |
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Authors: | Meletios A Dimopoulos Maria‐Victoria Mateos Paul G Richardson Rudolf Schlag Nuriet K Khuageva Ofer Shpilberg Martin Kropff Ivan Spicka Antonio Palumbo Ka Lung Wu Dixie‐Lee Esseltine Kevin Liu William Deraedt Andrew Cakana Helgi Van De Velde Jesús F San Miguel |
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Institution: | 1. School of Medicine, University of Athens, Athens, Greece;2. Hospital Universitario Salamanca, CIC, IBMCC (USAL‐CSIC), Salamanca, Spain;3. Dana‐Farber Cancer Institute, Boston, MA, USA;4. Praxisklinik Dr. Schlag, Würzburg, Germany;5. SP Botkin Moscow City Clinical Hospital, Russian Federation;6. Rabin Medical Center, Petah‐Tiqva, Israel;7. University of Münster, Münster, Germany;8. University Hospital, Prague, Czech Republic;9. Universita di Torino, Torino, Italy;10. Myeloma Study Group, Belgian Hematological Society, Brussels, Belgium;11. Millennium Pharmaceuticals, Inc., Cambridge, MA, USA;12. Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Raritan, NJ, USA;13. Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium;14. Johnson & Johnson Pharmaceutical Research and Development, High Wycombe, UK |
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Abstract: | 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/m2, days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1–4, and days 1, 8, 22, 29, cycles 5–9; melphalan 9 mg/m2, days 1–4, cycles 1–9; and prednisone 60 mg/m2, 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/m2. 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. (Clinicaltrials.gov identifier: NCT00111319). |
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Keywords: | peripheral neuropathy multiple myeloma subanalysis VISTA phase 3 bortezomib |
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