Display options
Cite
Tzogani K, Florez B, Markey G, et al. European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. ESMO Open. 2019;4(5):e000570doi: 10.1136/esmoopen-2019-000570.
Tzogani, K., Florez, B., Markey, G., Caleno, M., Olimpieri, O. M., Melchiorri, D., Hovgaard, D. J., Sarac, S. B., Penttilä, K., Lapveteläinen, T., Salmonson, T., Bergh, J., Gisselbrecht, C., & Pignatti, F. (2019). European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. ESMO open, 4(5), e000570. https://doi.org/10.1136/esmoopen-2019-000570
Tzogani, Kyriaki, et al. "European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy." ESMO open vol. 4,5 (2019): e000570. doi: https://doi.org/10.1136/esmoopen-2019-000570
Tzogani K, Florez B, Markey G, Caleno M, Olimpieri OM, Melchiorri D, Hovgaard DJ, Sarac SB, Penttilä K, Lapveteläinen T, Salmonson T, Bergh J, Gisselbrecht C, Pignatti F. European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. ESMO Open. 2019 Sep 08;4(5):e000570. doi: 10.1136/esmoopen-2019-000570. eCollection 2019. PMID: 31555488; PMCID: PMC6735670.
Copy Download .nbib Format: NLM
Share it on

ESMO Open. 2019 Sep 08;4(5):e000570. doi: 10.1136/esmoopen-2019-000570. eCollection 2019.

European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

ESMO open

Kyriaki Tzogani, Beatriz Florez, Greg Markey, Mariapaola Caleno, Odoardo Maria Olimpieri, Daniela Melchiorri, Doris Johanna Hovgaard, Sinan Bardakci Sarac, Karri Penttilä, Tuomo Lapveteläinen, Tomas Salmonson, Jonas Bergh, Christian Gisselbrecht, Francesco Pignatti

Affiliations

  1. European Medicines Agency, Amsterdam, The Netherlands.
  2. MHRA, London, UK.
  3. AIFA, Roma, Italy.
  4. Dip. Physiology and Pharmacology, V. Erspamer, University of Rome La Sapienza, Roma, Italy.
  5. Laegemiddelstyrelsen, Kobenhavn, Denmark.
  6. Finnish Medicines Agency Fimea, Helsinki, Finland.
  7. Lakemedelsverket, Uppsala, Sweden.
  8. Radiumhemmet Microbiology and Tumorbiology Center, Karolinska University Hospital, Stockholm, Sweden.
  9. Institut d'Hématologie, Hôpital Saint Louis Paris Diderot Université, Hospital Saint-Louis, Paris, France.

PMID: 31555488 PMCID: PMC6735670 DOI: 10.1136/esmoopen-2019-000570

Abstract

On 21 November 2016, the European Commission issued a marketing authorisation valid throughout the European Union for ixazomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Ixazomib was evaluated in one, randomised, double-blind, phase III study comparing ixazomib plus lenalidomide and dexamethasone (n=360; ixazomib arm) versus placebo plus lenalidomide and dexamethasone (n=362; placebo arm) in adult patients with relapsed and/or refractory multiple myeloma who had received at least one prior therapy. The median progression-free survival (PFS) in the intent-to-treat population was 20.6 months in patients treated with ixazomib compared with 14.7 months for patients in the placebo arm (stratified HR=0.742, 95% CI 0.587 to 0.939, stratified p-value=0.012). The most frequently reported adverse reactions (≥20%) within the ixazomib and placebo arms were diarrhoea (42% vs 36%), constipation (34% vs 25%), thrombocytopaenia (28% vs 14%), peripheral neuropathy (28% vs 21%), nausea (26% vs 21%), peripheral oedema (25% vs 18%), vomiting (22% vs 11%) and back pain (21% vs 16%). The scientific review concluded that the gain in PFS of 5.9 months observed with ixazomib was considered clinically meaningful. Concerning the possible uncertainty about the magnitude of the effect, this uncertainty was acceptable given the favourable toxicity profile, and considering that ixazomib is the first agent to allow oral triple combination therapy in this patient population which represents a therapeutic innovation in terms of convenience for patients. Therefore, the benefit-risk for ixazomib in combination with lenalidomide and dexamethasone was considered positive, although the efficacy evidence was not as comprehensive as normally required.

Keywords: EMA; European Medicines Agency; ixazomib; multiple myeloma

Conflict of interest statement

Competing interests: Jonas Bergh:Research grants for academic clinical studies/ molecular marker spin-off to Karolinska University Hospital and/or Karolinska Institutet from Amgen, AstraZeneca, Bayer,

References

  1. Am J Hematol. 2011 Jan;86(1):57-65 - PubMed
  2. Blood. 2011 May 5;117(18):4691-5 - PubMed
  3. Clin Cancer Res. 2011 Aug 15;17(16):5311-21 - PubMed
  4. Blood. 2011 Oct 27;118(17):4519-29 - PubMed
  5. Blood. 2014 Aug 14;124(7):1047-55 - PubMed
  6. Blood. 2014 Aug 14;124(7):1038-46 - PubMed
  7. Lancet Oncol. 2014 Dec;15(13):1503-1512 - PubMed
  8. N Engl J Med. 2016 Apr 28;374(17):1621-34 - PubMed

Publication Types