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Erschienen in: Targeted Oncology 4/2017

28.06.2017 | Adis Drug Evaluation

Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma

verfasst von: Zaina T. Al-Salama, Karly P. Garnock-Jones, Lesley J. Scott

Erschienen in: Targeted Oncology | Ausgabe 4/2017

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Abstract

The oral proteasome inhibitor ixazomib (Ninlaro®) is approved in the USA, EU and Japan in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. In adults with relapsed and/or refractory MM who had received one to three prior therapies, progression-free survival (PFS) was significantly prolonged in patients who received the ixazomib- versus placebo-based triple therapy in the pivotal, global TOURMALINE-MM1 trial and its regional expansion (China continuation study). A significantly longer time to progression and favourable hazard ratios for PFS were observed across all prespecified subgroups, including patients with high cytogenetic risk. Overall response was achieved in a significantly higher proportion of patients receiving ixazomib- than placebo-based treatment. Ixazomib had a manageable tolerability profile in patients with MM. Ixazomib is the first orally-administered proteasome inhibitor approved for patients with MM, and in combination with lenalidomide and dexamethasone represents an important new option for use in patients with relapsed and/or refractory MM who have previously received at least one prior therapy.
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Literatur
1.
3.
Zurück zum Zitat Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; doi:10.1093/annonc/mdx096. Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; doi:10.​1093/​annonc/​mdx096.
5.
Zurück zum Zitat Muz B, Ghazarian RN, Ou M, et al. Spotlight on ixazomib: potential in the treatment of multiple myeloma. Drug Des Devel Ther. 2016;10:217–26.PubMedPubMedCentral Muz B, Ghazarian RN, Ou M, et al. Spotlight on ixazomib: potential in the treatment of multiple myeloma. Drug Des Devel Ther. 2016;10:217–26.PubMedPubMedCentral
6.
Zurück zum Zitat Chng WJ, Dispenzieri A, Chim CS, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28(2):269–77.CrossRefPubMed Chng WJ, Dispenzieri A, Chim CS, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28(2):269–77.CrossRefPubMed
10.
Zurück zum Zitat Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010;70(5):1970–80.CrossRefPubMed Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010;70(5):1970–80.CrossRefPubMed
11.
Zurück zum Zitat Chauhan D, Tian Z, Zhou B, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res. 2011;17(16):5311–21.CrossRefPubMedPubMedCentral Chauhan D, Tian Z, Zhou B, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res. 2011;17(16):5311–21.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Gupta N, Huh Y, Hutmacher MM, et al. Integrated nonclinical and clinical risk assessment of the investigational proteasome inhibitor ixazomib on the QTc interval in cancer patients. Cancer Chemother Pharmacol. 2015;76(3):507–16.CrossRefPubMed Gupta N, Huh Y, Hutmacher MM, et al. Integrated nonclinical and clinical risk assessment of the investigational proteasome inhibitor ixazomib on the QTc interval in cancer patients. Cancer Chemother Pharmacol. 2015;76(3):507–16.CrossRefPubMed
13.
Zurück zum Zitat Kumar SK, Bensinger WI, Zimmerman TM, et al. Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. Blood. 2014;124(7):1047–55.CrossRefPubMedPubMedCentral Kumar SK, Bensinger WI, Zimmerman TM, et al. Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. Blood. 2014;124(7):1047–55.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Gupta N, Diderichsen PM, Hanley MJ, et al. Population pharmacokinetic analysis of ixazomib, an oral proteasome inhibitor, including data from the phase III TOURMALINE-MM1 study to inform labelling. Clin Pharmacokinet. 2017; doi:10.1007/s40262-017-0526-4. Gupta N, Diderichsen PM, Hanley MJ, et al. Population pharmacokinetic analysis of ixazomib, an oral proteasome inhibitor, including data from the phase III TOURMALINE-MM1 study to inform labelling. Clin Pharmacokinet. 2017; doi:10.​1007/​s40262-017-0526-4.
15.
Zurück zum Zitat Gupta N, Hanley MJ, Venkatakrishnan K, et al. The effect of a high-fat meal on the pharmacokinetics of ixazomib, an oral proteasome inhibitor, in patients with advanced solid tumors or lymphoma. J Clin Pharmacol. 2016;56(10):1288–95.CrossRefPubMedPubMedCentral Gupta N, Hanley MJ, Venkatakrishnan K, et al. The effect of a high-fat meal on the pharmacokinetics of ixazomib, an oral proteasome inhibitor, in patients with advanced solid tumors or lymphoma. J Clin Pharmacol. 2016;56(10):1288–95.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Gupta N, Zhang S, Pusalkar S, et al. A phase I mass balance study of ixazomib, an oral proteasome inhibitor (PI), using accelerator mass spectrometry (AMS) in patients with advanced solid tumors [abstract no. PI-040]. Clin Pharmacol Ther. 2017;101(Suppl 1):S30. Gupta N, Zhang S, Pusalkar S, et al. A phase I mass balance study of ixazomib, an oral proteasome inhibitor (PI), using accelerator mass spectrometry (AMS) in patients with advanced solid tumors [abstract no. PI-040]. Clin Pharmacol Ther. 2017;101(Suppl 1):S30.
18.
Zurück zum Zitat Gupta N, Hanley MJ, Venkatakrishnan K, et al. Pharmacokinetics of ixazomib, an oral proteasome inhibitor, in solid tumour patients with moderate or severe hepatic impairment. Br J Clin Pharmacol. 2016;82(3):728–38.CrossRefPubMedPubMedCentral Gupta N, Hanley MJ, Venkatakrishnan K, et al. Pharmacokinetics of ixazomib, an oral proteasome inhibitor, in solid tumour patients with moderate or severe hepatic impairment. Br J Clin Pharmacol. 2016;82(3):728–38.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Gupta N, Hanley MJ, Harvey RD, et al. A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis. Br J Haematol. 2016;174(5):748–59.CrossRefPubMedPubMedCentral Gupta N, Hanley MJ, Harvey RD, et al. A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis. Br J Haematol. 2016;174(5):748–59.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Suzuki K, Handa H, Chou T, et al. Phase 1 study of ixazomib alone or combined with lenalidomide-dexamethasone in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol. 2017;105(4):445–52.CrossRefPubMed Suzuki K, Handa H, Chou T, et al. Phase 1 study of ixazomib alone or combined with lenalidomide-dexamethasone in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol. 2017;105(4):445–52.CrossRefPubMed
21.
Zurück zum Zitat Gupta N, Goh YT, Min C-K, et al. Pharmacokinetics and safety of ixazomib plus lenalidomide–dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study. J Hematol Oncol. 2015;8(1):103.CrossRefPubMedPubMedCentral Gupta N, Goh YT, Min C-K, et al. Pharmacokinetics and safety of ixazomib plus lenalidomide–dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study. J Hematol Oncol. 2015;8(1):103.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17):1621–34.CrossRefPubMed Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17):1621–34.CrossRefPubMed
23.
Zurück zum Zitat Richardson PG, Avet-Loiseau H, Palumbo A, et al. Efficacy and safety of ixazomib plus lenalidomide-dexamethasone (IRd) vs placebo-rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM) by cytogenetic risk status in the global phase III TOURMALINE-MM1 study [abstract no. 8018 plus poster]. J Clin Oncol. 2016;34(Suppl). Richardson PG, Avet-Loiseau H, Palumbo A, et al. Efficacy and safety of ixazomib plus lenalidomide-dexamethasone (IRd) vs placebo-rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM) by cytogenetic risk status in the global phase III TOURMALINE-MM1 study [abstract no. 8018 plus poster]. J Clin Oncol. 2016;34(Suppl).
24.
Zurück zum Zitat Hou J, Jin J, Xu Y, et al. Improved PFS and OS with ixazomib plus lenalidomide-dexamethasone (IRd) vs placebo-Rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM): final data from phase 3 China continuation of TOURMALINE-MM1 [abstract PS-119]. In: 16th International Myeloma Workshop. 2017. Hou J, Jin J, Xu Y, et al. Improved PFS and OS with ixazomib plus lenalidomide-dexamethasone (IRd) vs placebo-Rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM): final data from phase 3 China continuation of TOURMALINE-MM1 [abstract PS-119]. In: 16th International Myeloma Workshop. 2017.
25.
Zurück zum Zitat Hou J, Jin J, Xu Y, et al. Ixazomib plus lenalidomide-dexamethasone (IRd) vs placebo-Rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM): China continuation of TOURMALINE-MM1 [abstract no. 8036 plus poster]. J Clin Oncol. 2016;34(Suppl). Hou J, Jin J, Xu Y, et al. Ixazomib plus lenalidomide-dexamethasone (IRd) vs placebo-Rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM): China continuation of TOURMALINE-MM1 [abstract no. 8036 plus poster]. J Clin Oncol. 2016;34(Suppl).
26.
Zurück zum Zitat Data on file, Takeda Pharmaceutical Company Limited, 2017. Data on file, Takeda Pharmaceutical Company Limited, 2017.
27.
Zurück zum Zitat Mateos M-V, Masszi T, Grzasko N, et al. Impact of prior therapy on efficacy and safety of oral ixazomib-lenalidomide-dexamethasone (IRd) vs placebo-Rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM) in TOURMALINE-MM1 [abstract no. 8039 plus poster]. J Clin Oncol. 2016;34(Suppl). Mateos M-V, Masszi T, Grzasko N, et al. Impact of prior therapy on efficacy and safety of oral ixazomib-lenalidomide-dexamethasone (IRd) vs placebo-Rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM) in TOURMALINE-MM1 [abstract no. 8039 plus poster]. J Clin Oncol. 2016;34(Suppl).
28.
Zurück zum Zitat National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: multiple myeloma (version 2.2017). 2016. http://www.nccn.org. Accessed 22 May 2017. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: multiple myeloma (version 2.2017). 2016. http://​www.​nccn.​org. Accessed 22 May 2017.
Metadaten
Titel
Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma
verfasst von
Zaina T. Al-Salama
Karly P. Garnock-Jones
Lesley J. Scott
Publikationsdatum
28.06.2017
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 4/2017
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-017-0504-7

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