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Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature.

Abstract：

BACKGROUND:Bortezomib is active in heavily pretreated multiple myeloma patients; the dose-limiting toxicity is peripheral neuropathy (PN). METHODS:The authors retrospectively reviewed the incidence, severity, and risk factors for PN in 78 patients who received bortezomib. The median age was 57 years (range, 33-80 years), 62% of patients were men, and 37% of patients were African Americans. Seventeen patients (22%) had diabetes mellitus (DM), and 66 patients (85%) had received thalidomide. Before bortezomib treatment, 37% of the patients reported subjective, grade 1 or 2 PN. Patients received bortezomib alone (n = 10 patients) plus dexamethasone (n = 36 patients) and thalidomide (n = 20 patients) or chemotherapy (n = 12 patients). PN affected 52% of patients, including grade 3 and 4 PN in 15% and 7%, respectively. RESULTS:Twelve patients stopped bortezomib because of side effects that included PN (n = 9 patients), diarrhea (n = 2 patients) and cytomegalovirus pneumonia (n = 1 patient); 11 patients had dose reductions because of PN. Grade 4 PN affected 6 patients (sensory, n = 4 patients; motor/sensory, n = 2 patients). The onset of grade 4 PN was sudden rather than cumulative. Factors that were predictive of PN grade were baseline PN (P = .002), prior thalidomide use (P = .03), and the presence of DM (P = .03). Multiple myeloma responses included complete, near complete, and partial responses in 5% of patients, 10% of patients, and 27% of patients, respectively. Responses were independent of PN and of whether bortezomib was combined with chemotherapy or thalidomide. Patients remained on therapy longer for a median of 5 cycles (range, 2-36 cycles) when they received bortezomib plus thalidomide versus 3 cycles (range, 1-19 cycles) for the other combinations. PN therapy was mostly supportive. It was noteworthy that 6 of 9 patients with PN who received lenalidomide as salvage therapy after bortezomib had significant improvement in their symptoms. CONCLUSIONS:The risk of bortezomib-related PN was greater in patients who had PN and DM at baseline. The authors concluded that an unexpected, symptomatic improvement of PN on lenalidomide is worth further investigation.

journal_name

Cancer

journal_title

Cancer

authors

Badros A,Goloubeva O,Dalal JS,Can I,Thompson J,Rapoport AP,Heyman M,Akpek G,Fenton RG

doi

10.1002/cncr.22921

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

1042-9

issue

eissn

0008-543X

issn

1097-0142

journal_volume

110

pub_type

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Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature.