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Impact of concomitant dexamethasone dosing schedule on bortezomib‐induced peripheral neuropathy in multiple myeloma
Author(s) -
Kumar Shaji K.,
Laubach Jacob P.,
Giove Thomas J.,
Quick Maureen,
Neuwirth Rachel,
Yung Godwin,
Rajkumar S. Vincent,
Richardson Paul G.
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14754
Subject(s) - bortezomib , medicine , dosing , dexamethasone , multiple myeloma , concomitant , thalidomide , peripheral neuropathy , proteasome inhibitor , gastroenterology , oncology , endocrinology , diabetes mellitus
Summary Peripheral neuropathy ( PN ) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib‐induced PN (Bi PN ) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce Bi PN incidence and/or severity. We retrospectively analysed PN rates from 32 studies (2697 patients with previously untreated multiple myeloma) incorporating bortezomib and differing dexamethasone schedules: partnered dosing (days of and after bortezomib), weekly dosing, and other dosing schedules (e.g. days 1–4, 8–11). Pooled overall PN rates were 45·5%, 63·9%, and 47·5%, respectively, with 5·3%, 11·0%, and 9·6% grade ≥3. Adjusting for potential confounders (age, gender, presence of thalidomide, bortezomib treatment duration), PN rates in patients on partnered dosing schedules appeared lower than in patients on weekly or other dosing schedules. Analyses conducted using patient‐level data suggest that cumulative dexamethasone dose, a potential confounding factor, is unlikely to have influenced the analyses. Findings were similar in a separate pooled analysis excluding data from regimens incorporating thalidomide, when pooled overall PN rates were 50·1%, 63·9%, and 48·3%, respectively, with 4·2%, 11·0%, and 8·6% grade ≥3. These findings suggest that partnered dexamethasone dosing may result in less severe Bi PN compared with alternative dexamethasone dosing schedules.