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Drug Evaluation

An overview of the role of carfilzomib in the treatment of multiple myeloma

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Pages 1883-1897 | Received 05 Sep 2017, Accepted 09 Nov 2017, Published online: 20 Nov 2017

References

  • Moreau P, Richardson PG, Cavo M, et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood. 2012 Aug 2;120(5):947–959. PubMed PMID: 22645181; PubMed Central PMCID: PMCPMC4123429.
  • Dou QP, Zonder JA. Overview of proteasome inhibitor-based anti-cancer therapies: perspective on bortezomib and second generation proteasome inhibitors versus future generation inhibitors of ubiquitin-proteasome system. Curr Cancer Drug Targets. 2014;14(6): 517–536. PubMed PMID: 25092212; PubMed Central PMCID: PMCPMC4279864.
  • Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26;348(26):2609–2617. PubMed PMID: 12826635.
  • Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005 Jun 16;352(24):2487–2498. PubMed PMID: 15958804.
  • Richardson PG, Briemberg H, Jagannath S, et al. Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol. 2006 Jul 1;24(19):3113–3120. PubMed PMID: 16754936.
  • Meng L, Mohan R, Kwok BH, et al. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc Natl Acad Sci USA. 1999 Aug 31;96(18):10403–10408. PubMed PMID: 10468620; PubMed Central PMCID: PMCPMC17900.
  • Ziogas DC, Terpos E, Kastritis E, et al. Carfilzomib for treating myeloma. Expert Opin Orphan Drugs. 2016;4(9):989–999.
  • Franken B, van de Donk NW, Cloos JC, et al. A clinical update on the role of carfilzomib in the treatment of relapsed or refractory multiple myeloma. Ther Adv Hematol. 2016 Dec;7(6):330–344. PubMed PMID: 27904737; PubMed Central PMCID: PMCPMC5089326.
  • Manasanch EE, Korde N, Zingone A, et al. The proteasome: mechanisms of biology and markers of activity and response to treatment in multiple myeloma. Leuk Lymphoma. 2014 Aug;55(8):1707–1714. PubMed PMID: 24261677.
  • Adams J. The proteasome: a suitable antineoplastic target. Nat Rev Cancer. 2004 May;4(5):349–360. PubMed PMID: 15122206.
  • Obeng EA, Carlson LM, Gutman DM, et al. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006 Jun 15;107(12):4907–4916. PubMed PMID: 16507771; PubMed Central PMCID: PMCPMC1895817.
  • Kortuem KM, Stewart AK. Carfilzomib. Blood. 2013 Feb 7;121(6):893–897. PubMed PMID: 23393020.
  • Demo SD, Kirk CJ, Aujay MA, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007 Jul 1;67(13):6383–6391. PubMed PMID: 17616698.
  • Wang Z, Yang J, Kirk C, et al. Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib. Drug Metab Dispos. 2013 Jan;41(1):230–237. PubMed PMID: 23118326.
  • Kuhn DJ, Chen Q, Voorhees PM, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281–3290. PubMed PMID: 17591945; PubMed Central PMCID: PMCPMC2200918.
  • Muchtar E, Gertz MA, Magen H. A practical review on carfilzomib in multiple myeloma. Eur J Haematol. 2016 Jun;96(6):564–577. PubMed PMID: 26893241.
  • Kuhn DJ, Hunsucker SA, Chen Q, et al. Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and nonspecific proteasome inhibitors. Blood. 2009 May 7;113(19):4667–4676. PubMed PMID: 19050304; PubMed Central PMCID: PMCPMC2680370.
  • Accardi F, Toscani D, Bolzoni M, et al. Mechanism of action of bortezomib and the new proteasome inhibitors on myeloma cells and the bone microenvironment: impact on myeloma-induced alterations of bone remodeling. Biomed Res Int. 2015. 2015:172458. PubMed PMID: 26579531; PubMed Central PMCID: PMCPMC4633537.
  • Alsina M, Trudel S, Furman RR, et al. A phase I single-agent study of twice-weekly consecutive-day dosing of the proteasome inhibitor carfilzomib in patients with relapsed or refractory multiple myeloma or lymphoma. Clin Cancer Res. 2012 Sep 1;18(17):4830–4840. PubMed PMID: 22761464.
  • Lee SJ, Levitsky K, Parlati F, et al. Clinical activity of carfilzomib correlates with inhibition of multiple proteasome subunits: application of a novel pharmacodynamic assay. Br J Haematol. 2016 Apr 12. PubMed PMID: 27071340. DOI:10.1111/bjh.14014.
  • Besse A, Stolze SC, Rasche L, et al. Carfilzomib resistance due to ABCB1/MDR1 overexpression is overcome by nelfinavir and lopinavir in multiple myeloma. Leukemia. 2017 Jul 5 PubMed PMID: 28676669. DOI:10.1038/leu.2017.212.
  • Soriano GP, Besse L, Li N, et al. Proteasome inhibitor-adapted myeloma cells are largely independent from proteasome activity and show complex proteomic changes, in particular in redox and energy metabolism. Leukemia. 2016 Nov;30(11):2198–2207. PubMed PMID: 27118406; PubMed Central PMCID: PMCPMC5097071.
  • Hawley TS, Riz I, Yang W, et al. Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1. Am J Hematol. 2013 Apr;88(4):265–272. PubMed PMID: 23475625; PubMed Central PMCID: PMCPMC3608751.
  • Kuhn DJ, Orlowski RZ, Bjorklund CC. Second generation proteasome inhibitors: carfilzomib and immunoproteasome-specific inhibitors (IPSIs). Curr Cancer Drug Targets. 2011 Mar;11(3):285–295. PubMed PMID: 21247387.
  • Squifflet P, Michiels S, Siegel D, et al. Relationship between carfilzomib dose and efficacy outcomes in patients with relapsed and/or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2015 Nov;15(11):680–686. PubMed PMID: 26482107.
  • Papadopoulos KP, Siegel DS, Vesole DH, et al. Phase I study of 30-minute infusion of carfilzomib as single agent or in combination with low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma. J Clin Oncol. 2015 Mar 1;33(7):732–739. PubMed PMID: 25225420.
  • Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015 Jan 8;372(2):142–152. PubMed PMID: 25482145.
  • Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016 Jan;17(1):27–38. PubMed PMID: 26671818.
  • Berenson JR, Cartmell A, Bessudo A, et al. CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma. Blood. 2016 Jun 30;127(26):3360–3368. PubMed PMID: 27207788.
  • O’Connor OA, Stewart AK, Vallone M, et al. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin Cancer Res. 2009 Nov 15;15(22):7085–7091. PubMed PMID: 19903785; PubMed Central PMCID: PMCPMC4019989.
  • Jagannath S, Vij R, Stewart AK, et al. An open-label single-arm pilot phase II study (PX-171-003-A0) of low-dose, single-agent carfilzomib in patients with relapsed and refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):310–318. PubMed PMID: 23040437.
  • Siegel DS, Martin T, Wang M, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012 Oct 4;120(14):2817–2825. PubMed PMID: 22833546; PubMed Central PMCID: PMCPMC4123387.
  • Vij R, Wang M, Kaufman JL, et al. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012 Jun 14;119(24):5661–5670. PubMed PMID: 22555973; PubMed Central PMCID: PMCPMC4123327.
  • Wang M, Martin T, Bensinger W, et al. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood. 2013 Oct 31;122(18):3122–3128. PubMed PMID: 24014245; PubMed Central PMCID: PMCPMC3814729.
  • Dimopoulos MA, Stewart AK, Masszi T, et al. Carfilzomib, lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorised by age: secondary analysis from the phase 3 ASPIRE study. Br J Haematol. 2017 May;177(3):404–413. PubMed PMID: 28211560; PubMed Central PMCID: PMCPMC5412871.
  • Dimopoulos MA, Goldschmidt H, Niesvizky R, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Aug 23. PubMed PMID: 28843768. DOI:10.1016/S1470-2045(17)30578-8.
  • Shah JJ, Stadtmauer EA, Abonour R, et al. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015 Nov 12;126(20):2284–2290. PubMed PMID: 26384354; PubMed Central PMCID: PMCPMC4643003.
  • Berdeja JG, Hart LL, Mace JR, et al. Phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma. Haematologica. 2015 May;100(5):670–676. PubMed PMID: 25710456; PubMed Central PMCID: PMCPMC4420216.
  • Vesole DH, Bilotti E, Richter JR, et al. Phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Br J Haematol. 2015 Oct;171(1):52–59. PubMed PMID: 26018491.
  • Hajek R, Masszi T, Petrucci MT, et al. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia. 2017 Jan;31(1):107–114. PubMed PMID: 27416912; PubMed Central PMCID: PMCPMC5220126.
  • Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012 Aug 30;120(9):1801–1809. PubMed PMID: 22665938; PubMed Central PMCID: PMCPMC5162553.
  • Sonneveld P, Asselbergs E, Zweegman S, et al. Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015 Jan 15;125(3):449–456. PubMed PMID: 25398935; PubMed Central PMCID: PMCPMC4300390.
  • Bringhen S, Petrucci MT, Larocca A, et al. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood. 2014 Jul 3;124(1):63–69. PubMed PMID: 24855212.
  • Moreau P, Kolb B, Attal M, et al. Phase 1/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma. Blood. 2015 May 14;125(20):3100–3104. PubMed PMID: 25784682.
  • Mikhael JR, Reeder CB, Libby EN, et al. Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma. Br J Haematol. 2015 Apr;169(2):219–227. PubMed PMID: 25683772; PubMed Central PMCID: PMCPMC4521972.
  • Korde N, Roschewski M, Zingone A, et al. Treatment with carfilzomib-lenalidomide-dexamethasone with lenalidomide extension in patients with smoldering or newly diagnosed multiple myeloma. JAMA Oncol. 2015 Sep;1(6):746–754. PubMed PMID: 26181891.
  • Siegel D, Martin T, Nooka A, et al. Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies. Haematologica. 2013 Nov;98(11):1753–1761. PubMed PMID: 23935022; PubMed Central PMCID: PMCPMC3815177.
  • Lendvai N, Hilden P, Devlin S, et al. A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma. Blood. 2014 Aug 7;124(6):899–906. PubMed PMID: 24963043; PubMed Central PMCID: PMCPMC4624439.
  • Dimopoulos MA, Rousou M, Gavriatopoulou M, et al. Cardiac and renal complications of carfilzomib in patients with multiple myeloma [Regular]. Blood Advances. 2017 Jan 20;1(7):449–454.
  • Rosenthal A, Luthi J, Belohlavek M, et al. Carfilzomib and the cardiorenal system in myeloma: an endothelial effect? Blood Cancer J. 2016;6:e384. PubMed PMID: 26771810; PubMed Central PMCID: PMCPMC4742629.
  • Atrash S, Tullos A, Panozzo S, et al. Cardiac complications in relapsed and refractory multiple myeloma patients treated with carfilzomib. Blood Cancer J. 2015;5:e272. PubMed PMID: 25594159; PubMed Central PMCID: PMCPMC4314456.
  • Danhof S, Schreder M, Rasche L, et al. Real-life experience of preapproval carfilzomib-based therapy in myeloma - analysis of cardiac toxicity and predisposing factors. Eur J Haematol. 2015 Sep 2 PubMed PMID: 26331915. DOI:10.1111/ejh.12677.
  • Delforge M, Blade J, Dimopoulos MA, et al. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol. 2010 Nov;11(11):1086–1095. PubMed PMID: 20932799.
  • Cai X, Bhattacharyya S, Plitt A, et al. Management of posterior reversible encephalopathy syndrome induced by carfilzomib in a patient with multiple myeloma. J Clin Oncol. 2016 Jan 10;34(2):e1–e5. PubMed PMID: 24799479.
  • Dimopoulos MA, Sonneveld P, Leung N, et al. International myeloma working group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol. 2016 May 1;34(13):1544–1557. PubMed PMID: 26976420.
  • Quach H, White D, Spencer A, et al. Pharmacokinetics and safety of carfilzomib in patients with relapsed multiple myeloma and end-stage renal disease (ESRD): an open-label, single-arm, phase I study. Cancer Chemother Pharmacol. 2017 Jun;79(6):1067–1076. PubMed PMID: 28424963; PubMed Central PMCID: PMCPMC5438822.
  • Badros AZ, Vij R, Martin T, et al. Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety. Leukemia. 2013 Aug;27(8):1707–1714. PubMed PMID: 23364621; PubMed Central PMCID: PMCPMC3740399.
  • Palumbo A, Gay F, Cavallo F, et al. Continuous therapy versus fixed duration of therapy in patients with newly diagnosed multiple myeloma. J Clin Oncol. 2015 Oct 20;33(30):3459–3466. PubMed PMID: 26282661.
  • Berenson JR, Hilger JD, Yellin O, et al. Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy. Leukemia. 2014 Jul;28(7):1529–1536. PubMed PMID: 24429497.
  • Muchtar E, Gatt ME, Rouvio O, et al. Efficacy and safety of salvage therapy using carfilzomib for relapsed or refractory multiple myeloma patients: a multicentre retrospective observational study. Br J Haematol. 2016 Jan;172(1):89–96. PubMed PMID: 26567759.
  • Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood. 2007 Apr 15;109(8):3489–3495. PubMed PMID: 17209057.
  • Chng WJ, Dispenzieri A, Chim CS, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014 Feb;28(2):269–277. PubMed PMID: 23974982.
  • Chng WJ, Goldschmidt H, Dimopoulos MA, et al. Carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR. Leukemia. 2017 Jun;31(6):1368–1374. PubMed PMID: 28025582; PubMed Central PMCID: PMCPMC5467042.
  • Avet-Loiseau H, Fonseca R, Siegel D, et al. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma. Blood. 2016 Sep 1;128(9):1174–1180. PubMed PMID: 27439911; PubMed Central PMCID: PMCPMC5009511.

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