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

Kumar S, Moreau P, Hari P, Mateos MV, Ludwig H, Shustik C, Masszi T, Spencer A, Hajek R, Romeril K, Avivi I, Liberati AM, Minnema MC, Einsele H, Lonial S, Berg D, Lin J, Gupta N, Esseltine DL, Richardson PG (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 178

Pages Range: 571-582

Journal Issue: 4

DOI: 10.1111/bjh.14733

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.

Involved external institutions

Mayo Clinic United States (USA) (US) Universitätsklinikum Heidelberg Germany (DE) Froedtert Hospital United States (USA) (US) University of Salamanca / Universidad de Salamanca Spain (ES) Wilhelminenspital Austria (AT) McGill University Canada (CA) Semmelweis University / Semmelweis Egyetem Hungary (HU) Monash University Australia (AU) University Hospital Ostrava / Fakultní Nemocnice Ostrava Czech Republic (CZ) Wellington Hospital New Zealand (NZ) Tel Aviv University Israel (IL) Università degli Studi di Perugia Italy (IT) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Universitätsklinikum Würzburg Germany (DE) Emory University United States (USA) (US) Millennium Pharmaceuticals United States (USA) (US) Dana–Farber Cancer Institute United States (USA) (US)

How to cite

APA:

Kumar, S., Moreau, P., Hari, P., Mateos, M.-V., Ludwig, H., Shustik, C.,... 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

MLA:

Kumar, Shaji, et al. "Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma." British Journal of Haematology 178.4 (2017): 571-582.

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