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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
Author(s) -
Dimopoulos Meletios A.,
Mateos MariaVictoria,
Richardson Paul G.,
Schlag Rudolf,
Khuageva Nuriet K.,
Shpilberg Ofer,
Kropff Martin,
Spicka Ivan,
Palumbo Antonio,
Wu Ka Lung,
Esseltine DixieLee,
Liu Kevin,
Deraedt William,
Cakana Andrew,
Van De Velde Helgi,
San Miguel Jesús F.
Publication year - 2011
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2010.01533.x
Subject(s) - bortezomib , medicine , prednisone , melphalan , multiple myeloma , hazard ratio , gastroenterology , cumulative incidence , cumulative dose , peripheral neuropathy , creatinine , surgery , diabetes mellitus , transplantation , confidence interval , endocrinology
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. (Clinicaltrials.gov identifier: NCT00111319).