Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma

Shaji Kumar, Philippe Moreau, Parameswaran Hari, Maria Victoria Mateos, Heinz Ludwig, Chaim Shustik, T. Masszi, Andrew Spencer, Roman Hájek, Kenneth Romeril, Irit Avivi, Anna M. Liberati, Monique C. Minnema, Hermann Einsele, Sagar Lonial, Deborah Berg, Jianchang Lin, Neeraj Gupta, Dixie Lee Esseltine, Paul G. Richardson

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The oral proteasome inhibitor ixazomib is approved in the United States, European Union and other countries, in combination with oral lenalidomide and dexamethasone (Rd), for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on the global, randomised, double-blind, placebo-controlled Phase III TOURMALINE-MM1 study of ixazomib-Rd (IRd) versus placebo-Rd in patients with relapsed/refractory multiple myeloma. IRd resulted in a significant improvement in progression-free survival versus placebo-Rd (median: 20·6 vs. 14·7 months; hazard ratio 0·74). Common toxicities observed more commonly with IRd versus placebo-Rd were thrombocytopenia, nausea, vomiting, diarrhoea, constipation, rash, peripheral neuropathy, peripheral oedema and back pain; these were generally grade 1/2 in severity except for thrombocytopenia (19% vs. 9% grade 3/4), which appeared manageable and reversible, with no differences between arms in significant bleeding or dose discontinuations. No cumulative toxicities were observed, indicating the potential feasibility of long-term IRd treatment. Safety data from TOURMALINE-MM1 are reviewed and guidance for managing clinically relevant adverse events associated with IRd is provided. Most toxicities were manageable with supportive care and dose delays or reductions as needed. Clinicians should be aware of and understand these potential side effects to optimise and prolong patient benefit.

Original languageEnglish
Pages (from-to)571-582
Number of pages12
JournalBritish Journal of Haematology
Volume178
Issue number4
DOIs
Publication statusPublished - Aug 1 2017

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Multiple Myeloma
Dexamethasone
Placebos
Thrombocytopenia
Proteasome Inhibitors
Peripheral Nervous System Diseases
European Union
Constipation
Back Pain
Exanthema
Nausea
Disease-Free Survival
Vomiting
lenalidomide
ixazomib
Diarrhea
Edema
Therapeutics
Hemorrhage
Safety

Keywords

  • dosing
  • ixazomib
  • multiple myeloma
  • proteasome inhibitor
  • toxicity

ASJC Scopus subject areas

  • Hematology

Cite this

Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma. / Kumar, Shaji; Moreau, Philippe; Hari, Parameswaran; Mateos, Maria Victoria; Ludwig, Heinz; Shustik, Chaim; Masszi, T.; Spencer, Andrew; Hájek, Roman; Romeril, Kenneth; Avivi, Irit; Liberati, Anna M.; Minnema, Monique C.; Einsele, Hermann; Lonial, Sagar; Berg, Deborah; Lin, Jianchang; Gupta, Neeraj; Esseltine, Dixie Lee; Richardson, Paul G.

In: British Journal of Haematology, Vol. 178, No. 4, 01.08.2017, p. 571-582.

Research output: Contribution to journalArticle

Kumar, S, Moreau, P, Hari, P, Mateos, MV, Ludwig, H, Shustik, C, Masszi, T, Spencer, A, Hájek, R, Romeril, K, Avivi, I, Liberati, AM, Minnema, MC, Einsele, H, Lonial, S, Berg, D, Lin, J, Gupta, N, Esseltine, DL & Richardson, PG 2017, 'Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma', British Journal of Haematology, vol. 178, no. 4, pp. 571-582. https://doi.org/10.1111/bjh.14733
Kumar, Shaji ; Moreau, Philippe ; Hari, Parameswaran ; Mateos, Maria Victoria ; Ludwig, Heinz ; Shustik, Chaim ; Masszi, T. ; Spencer, Andrew ; Hájek, Roman ; Romeril, Kenneth ; Avivi, Irit ; Liberati, Anna M. ; Minnema, Monique C. ; Einsele, Hermann ; Lonial, Sagar ; Berg, Deborah ; Lin, Jianchang ; Gupta, Neeraj ; Esseltine, Dixie Lee ; Richardson, Paul G. / Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma. In: British Journal of Haematology. 2017 ; Vol. 178, No. 4. pp. 571-582.
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