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

Shaji K. Kumar, Philippe Moreau, Parameswaran Hari, Maria-Victoria Mateos, Heinz Ludwig, Chaim Shustik, Tamas 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

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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 2017

Keywords

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

Cite this

Kumar, S. K., Moreau, P., Hari, P., Mateos, M-V., Ludwig, H., Shustik, C., Masszi, T., Spencer, A., Hájek, R., Romeril, K., Avivi, I., Liberati, A. M., Minnema, M. C., Einsele, H., Lonial, S., Berg, D., Lin, J., Gupta, N., Esseltine, D-L., & Richardson, P. G. (2017). Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma. British Journal of Haematology, 178(4), 571-582. https://doi.org/10.1111/bjh.14733