Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma

Shaji K Kumar, Jacob P. Laubach, Thomas J. Giove, Maureen Quick, Rachel Neuwirth, Godwin Yung, S Vincent Rajkumar, Paul G. Richardson

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce BiPN 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 BiPN compared with alternative dexamethasone dosing schedules.

Original languageEnglish (US)
JournalBritish Journal of Haematology
DOIs
StateAccepted/In press - 2017

Fingerprint

Peripheral Nervous System Diseases
Multiple Myeloma
Dexamethasone
Appointments and Schedules
Thalidomide
Proteasome Inhibitors
Bortezomib
Inflammation
Incidence

Keywords

  • Bortezomib
  • Bortezomib-induced peripheral neuropathy
  • Dexamethasone
  • Multiple myeloma
  • Peripheral neuropathy

ASJC Scopus subject areas

  • Hematology

Cite this

Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma. / Kumar, Shaji K; Laubach, Jacob P.; Giove, Thomas J.; Quick, Maureen; Neuwirth, Rachel; Yung, Godwin; Rajkumar, S Vincent; Richardson, Paul G.

In: British Journal of Haematology, 2017.

Research output: Contribution to journalArticle

Kumar, Shaji K ; Laubach, Jacob P. ; Giove, Thomas J. ; Quick, Maureen ; Neuwirth, Rachel ; Yung, Godwin ; Rajkumar, S Vincent ; Richardson, Paul G. / Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma. In: British Journal of Haematology. 2017.
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abstract = "Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce BiPN 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 BiPN compared with alternative dexamethasone dosing schedules.",
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