The Role of Carfilzomib in Treatment of Newly Diagnosed Multiple Myeloma

References

• Ferlay J , SoerjomataramII, DikshitRet al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer136(5), e359–e386 (2014).
   PubMed Web of Science ®Google Scholar
• Howlader N , NooneA, KrapchoMet al. SEER Cancer Statistics Review, 1975–2012. Based on November 2014 SEER data submission, posted to the SEER web site, April 2015. National Cancer Institute, MD, USA (2015). http://seer.cancer.gov/csr/1975_2012/.
   Google Scholar
• Harousseau J , AttalM, Avet-loiseauH. The role of complete response in multiple myeloma. Blood114(15), 3139–3146 (2009).
   PubMed Web of Science ®Google Scholar
• Smith D , YongK. Advances in understanding prognosis in myeloma. Br. J. Haematol.175(3), 367–380 (2016).
   PubMed Web of Science ®Google Scholar
• Moreau P , HulinC, MacroMet al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood127(21), 2569–2574 (2016).
   PubMed Web of Science ®Google Scholar
• Kumar SK , FlinnI, RichardsonPGet al. Randomized, multicenter, Phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood119(19), 4375–4382 (2012).
   PubMed Web of Science ®Google Scholar
• Durie BGM , HoeringA, AbidiMHet al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, Phase 3 trial. Lancet389(10068), 519–527 (2017).
   PubMed Web of Science ®Google Scholar
• Rajkumar SV , KumarS. Multiple myeloma: diagnosis and treatment. Mayo Clin. Proc.91(1), 101–119 (2016).
   PubMed Web of Science ®Google Scholar
• Moreau P , San MiguelJ, SonneveldPet al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol.28, iv52–iv61 (2017).
   PubMed Web of Science ®Google Scholar
• Kumar SK , CallanderNS, AlsinaMet al. Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology. J. Natl Compr. Canc. Netw.15(2), 230–269 (2017).
   PubMed Web of Science ®Google Scholar
• Herndon TM , DeisserothA, KaminskasEet al. US Food and Drug Administration Approval: carfilzomib for the treatment of multiple myeloma. Clin. Cancer Res.19(17), 4559–4563 (2013).
   PubMed Web of Science ®Google Scholar
• Alsina M , TrudelS, FurmanRRet 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.18(17), 4830–4840 (2012).
   PubMed Web of Science ®Google Scholar
• O’Connor OA , StewartAK, ValloneMet 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.15(22), 7085–7091 (2009).
   PubMed Web of Science ®Google Scholar
• Siegel DS , MartinT, WangMet al. A Phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood120(14), 2817–2825 (2012).
   PubMed Web of Science ®Google Scholar
• Vij R , WangM, KaufmanJLet 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. Blood119(24), 5661–5670 (2012).
   PubMed Web of Science ®Google Scholar
• Badros AZ , VijR, MartinTet al. Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety. Leukemia27(8), 1707–1714 (2013).
   PubMed Web of Science ®Google Scholar
• Wang M , MartinT, BensingerWet al. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood122(18), 3122–3128 (2013).
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA , MoreauP, PalumboAet 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.17(1), 27–38 (2016).
   PubMed Web of Science ®Google Scholar
• Stewart AK , RajkumarSV, DimopoulosMAet al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N. Engl. J. Med.372(2), 142–152 (2015).
   PubMed Web of Science ®Google Scholar
• Stewart AK , SiegelD, LudwigHet al. Overall survival (OS) of patients with relapsed/refractory multiple myeloma (RRMM) treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd): final analysis from the randomized Phase 3 Aspire trial. Blood130(Suppl. 1), 743–743 (2017).
   Google Scholar
• Brown S , HinsleyS, BallesterosMet al. The MUK five protocol: a Phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) versus cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refracto. BMC Hematol.16(1), 14 (2016).
   PubMedGoogle Scholar
• Bringhen S , PetrucciMT, LaroccaAet al. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, Phase 2 study. Blood124(1), 63–69 (2014).
   PubMed Web of Science ®Google Scholar
• Shah JJ , StadtmauerEA, AbonourRet al. A multi-center Phase I/II trial of carfilzomib and pomalidomide with dexamethasone (car-pom-D) in patients with relapsed/refractory multiple myeloma. Blood120(21) (2012).
   Web of Science ®Google Scholar
• Vincenz L , JagerR, O’DwyerM, SamaliA. Endoplasmic reticulum stress and the unfolded protein response: targeting the Achilles heel of multiple myeloma. Mol. Cancer Ther.12(6), 831–843 (2013).
   PubMed Web of Science ®Google Scholar
• Obeng EA , CarlsonLM, GutmanDM, HarringtonWJ, LeeKP, BoiseLH. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood107(12), 4907–4916 (2006).
   PubMed Web of Science ®Google Scholar
• Meister S , SchubertU, NeubertKet al. Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition. Cancer Res.67(4), 1783–1792 (2007).
   PubMed Web of Science ®Google Scholar
• Wang Z , YangJ, KirkCet al. Clinical pharmacokinetics, metabolism, and drug–drug interaction of carfilzomib. Drug Metab. Dispos.41(1), 230–237 (2013).
   PubMed Web of Science ®Google Scholar
• Demo SD , KirkCJ, AujayMAet al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res.67(13), 6383–6391 (2007).
   PubMed Web of Science ®Google Scholar
• Jakubowiak AJ , DytfeldD, GriffithKAet al. A Phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood120(9), 1801–1809 (2012).
   PubMed Web of Science ®Google Scholar
• Korde N , RoschewskiM, ZingoneAet al. Treatment with carfilzomib–lenalidomide–dexamethasone with lenalidomide extension in patients with smoldering or newly diagnosed multiple myeloma. JAMA Oncol.1(6), 746 (2015).
   PubMed Web of Science ®Google Scholar
• Kazandjian D , KordeNS, RoschewskiMet al. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma (NDMM) patients treated with carfilzomib (CFZ), lenalidomide (LEN), and dexamethasone (DEX) followed by 2 years of lenalidomide maintenance (CRd-R): updated results of a Phase 2 study. Blood128(22), 4527 LP–4527 (2016).
   Web of Science ®Google Scholar
• Zimmerman T , RajeNS, VijRet al. Final results of a Phase 2 trial of extended treatment (tx) with carfilzomib (CFZ), lenalidomide (LEN), and dexamethasone (KRd) plus autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (NDMM). Blood128(22), 675–675 (2016).
   Web of Science ®Google Scholar
• Roussel M , Lauwers-CancesV, RobillardNet al. Frontline therapy with carfilzomib, lenalidomide, and dexamethasone (KRd) induction followed by autologous stem cell transplantation, Krd consolidation and lenalidomide maintenance in newly diagnosed multiple myeloma (NDMM) patients: primary results of the Intergroupe Francophone Du MyéLome (IFM) Krd Phase II Study. Blood128(22), 1142–1142 (2016).
   Web of Science ®Google Scholar
• Boccia RV , BessudoA, AgajanianRet al. A multicenter, open-label, Phase 1b study of carfilzomib, cyclophosphamide, and dexamethasone in newly diagnosed multiple myeloma patients (CHAMPION-2). Clin. Lymphoma Myeloma Leuk.17(7), 433–437 (2017).
   PubMed Web of Science ®Google Scholar
• Bringhen S , D’AgostinoM, De PaoliLet al. Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma. Leukemia32(4), 979–985 (2018).
   PubMed Web of Science ®Google Scholar
• Bensinger WI , VescioR, GasparettoCet al. A multi-center Phase 1b, open-label, dose-finding pilot study to evaluate the combination of carfilzomib and cyclophosphamide with dexamethasone (CCyD) prior to autologous stem cell transplant (ASCT) in patients with transplant eligible newly diagnosed multiple myeloma. Blood124(21), 4739–4739 (2014).
   Web of Science ®Google Scholar
• Gay FM , Rota ScalabriniD, BelottiAet al. Carfilzomib–lenalidomide–dexamethasone (KRd) vs carfilzomib–cyclophosphamide–dexamethasone (KCd) induction: planned interim analysis of the randomized FORTE trial in newly diagnosed multiple myeloma (NDMM). J. Clin. Oncol.35(15 Suppl.), 8003 (2017).
   Google Scholar
• Leleu X , FouquetG, KarlinLet al. Carfilzomib weekly melphalan–prednisone in untreated elderly multiple myeloma: IFM2012-03. J. Clin. Oncol.35(15 Suppl.), 8004 (2017).
   Google Scholar
• Moreau P , KolbB, AttalMet al. Phase 1/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma. Blood125(20), 3100–3104 (2015).
   PubMed Web of Science ®Google Scholar
• San Miguel JF , SchlagR, KhuagevaNKet al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N. Engl. J. Med.359(9), 906–917 (2008).
   PubMed Web of Science ®Google Scholar
• Facon T , LeeJH, MoreauP. Phase 3 study (CLARION) of carfilzomib, melphalan, prednisone (KMP) v bortezomib, melphalan, prednisone (VMP) in newly diagnosed multiple myeloma (NDMM). Presented at: 16th International Myeloma Workshop. 1–4 March, New Delhi, India, (2017).
   Google Scholar
• Chari A , UsmaniSZ, KrishnanAet al. Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients with newly diagnosed multiple myeloma (MMY1001): updated results from an open-label, Phase 1b study. Blood130(Suppl. 1), 3110–3110 (2017).
   Google Scholar
• Wester R , van derH, oltB, AsselbergsEet al. Carfilzomib combined with thalidomide and low-dose dexamethasone for remission induction and consolidation in newly diagnosed, transplant eligible patients with multiple myeloma: the Carthadex trial. Blood130(Suppl. 1), 3141–3141 (2017).
   Google Scholar
• Mikhael JR , ReederCB, LibbyENet al. Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma. Br. J. Haematol.169(2), 219–227 (2015).
   PubMed Web of Science ®Google Scholar
• Chng W , DispenzieriA, ChimC-Set al. IMWG consensus on risk stratification in multiple myeloma. Leukemia28(2), 269–277 (2014).
   PubMed Web of Science ®Google Scholar
• Sonneveld P , Avet-LoiseauH, LonialSet al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood127(24), 2955–2962 (2016).
   PubMed Web of Science ®Google Scholar
• Sonneveld P , AsselbergsE, ZweegmanSet al. Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood125(3), 449–456 (2015).
   PubMed Web of Science ®Google Scholar
• Siegel D , MartinT, NookaAet al. Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 Phase II clinical studies. Haematologica98(11), 1753–1761 (2013).
   PubMed Web of Science ®Google Scholar
• Sheng Z , LiG, LiB, LiuY, WangL. Carfilzomib-containing combinations as frontline therapy for multiple myeloma: a meta-analysis of 13 trials. Eur. J. Haematol.98(6), 601–607 (2017).
   PubMed Web of Science ®Google Scholar
• Moreau P , PylypenkoH, GrosickiSet al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, Phase 3, non-inferiority study. Lancet Oncol.12(5), 431–440 (2011).
   PubMed Web of Science ®Google Scholar
• Richardson PG , DelforgeM, BeksacMet al. Management of treatment-emergent peripheral neuropathy in multiple myeloma. Leukemia26(4), 595–608 (2012).
   PubMed Web of Science ®Google Scholar
• Arastu-Kapur S , AnderlJL, KrausMet al. Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin. Cancer Res.17(9), 2734–2743 (2011).
   PubMed Web of Science ®Google Scholar
• Hasinoff BB , PatelD, WuX. Molecular mechanisms of the cardiotoxicity of the proteasomal-targeted drugs bortezomib and carfilzomib. Cardiovasc. Toxicol.17(3), 237–250 (2017).
   PubMed Web of Science ®Google Scholar
• Cole DC , FrishmanWH. Cardiovascular complications of proteasome inhibitors used in multiple myeloma. Cardiol. Rev. 26(3), 122–129 (2018).
   PubMed Web of Science ®Google Scholar
• Laubach JP , MoslehiJJ, FrancisSAet al. A retrospective analysis of 3954 patients in Phase 2/3 trials of bortezomib for the treatment of multiple myeloma: toward providing a benchmark for the cardiac safety profile of proteasome inhibition in multiple myeloma. Br. J. Haematol.178(4), 547–560 (2017).
   PubMed Web of Science ®Google Scholar
• Waxman A , ClasenS, HwangW, AlE. Carfilzomib-associated cardiovascular adverse events: a systematic review and meta-analysis. JAMA Oncol.e174519 (2017).
   Web of Science ®Google Scholar
• Chari A , HajjeD. Case series discussion of cardiac and vascular events following carfilzomib treatment: possible mechanism, screening, and monitoring. BMC Cancer14(1), 915 (2014).
   PubMedGoogle Scholar
• Danhof S , SchrederM, RascheL, StriflerS, EinseleH, KnopS. “Real-life” experience of preapproval carfilzomib-based therapy in myeloma – analysis of cardiac toxicity and predisposing factors. Eur. J. Haematol.97(1), 25–32 (2016).
   PubMed Web of Science ®Google Scholar
• Grandin EW , KyB, CornellRF, CarverJ, LenihanDJ. Patterns of cardiac toxicity associated with irreversible proteasome inhibition in the treatment of multiple myeloma. J. Card. Fail.21(2), 138–144 (2015).
   PubMed Web of Science ®Google Scholar
• Atrash S , TullosA, PanozzoSet al. Cardiac complications in relapsed and refractory multiple myeloma patients treated with carfilzomib. Blood Cancer J.5(1), e272–e272 (2015).
   PubMedGoogle Scholar
• Bringhen S , MinaR, PetrucciMTet al. Incidence and risk factors of cardiovascular adverse events in a large population of newly diagnosed, transplant-ineligible myeloma patients treated with carfilzomib. Haematologica102(102), Abstract E1247 (2017).
   Google Scholar
• Mina R , PetrucciMT, GiulianiNet al. Cardio-vascular toxicity in newly diagnosed, transplant-ineligible multiple myeloma patients treated with carfilzomib, cyclophosphamide and dexamethasone: results from an integrated analysis of 3 Phase I/II trials. Clin. Lymphoma Myeloma Leuk.17(1), e7 (2017).
   PubMed Web of Science ®Google Scholar
• Lendvai N , TsakosI, DevlinSMet al. Predictive biomarkers and practical considerations in the management of carfilzomib-associated cardiotoxicity. Leuk. Lymphoma59(8), 1981–1985 (2018).
   PubMed Web of Science ®Google Scholar
• Franken B , van de DonkNW, CloosJC, ZweegmanS, LokhorstHM. A clinical update on the role of carfilzomib in the treatment of relapsed or refractory multiple myeloma. Ther. Adv. Hematol.7(6), 330–344 (2016).
   PubMed Web of Science ®Google Scholar
• Muchtar E , GertzMA, MagenH. A practical review on carfilzomib in multiple myeloma. Eur. J. Haematol.96(6), 564–577 (2016).
   PubMed Web of Science ®Google Scholar
• Russell SD , LyonA, LenihanDJet al. Serial echocardiographic assessment of patients (Pts) with relapsed multiple myeloma (RMM) receiving carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd): a substudy of the Phase 3 Endeavor Trial (NCT01568866). Blood126(23), 4250–4250 (2015).
   Web of Science ®Google Scholar
• Ludwig H , DelforgeM, FaconTet al. Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. Leukemia32(7), 1542–1560 (2018)
   PubMed Web of Science ®Google Scholar
• Berenson JR , CartmellA, BessudoAet al. CHAMPION-1: a Phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma. Blood127(26), 3360–3368 (2016).
   PubMed Web of Science ®Google Scholar
• Moreau P , MateosM-V, BerensonJRet al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, Phase 3 study. Lancet Oncol. 19(7), 953–964 (2018).
   PubMed Web of Science ®Google Scholar
• Landgren O , DevlinS, BouladM, MailankodyS. Role of MRD status in relation to clinical outcomes in newly diagnosed multiple myeloma patients: a meta-analysis. Bone Marrow Transplant.51(12), 1565–1568 (2016).
   PubMed Web of Science ®Google Scholar
• Munshi N , Avet-LoiseauH, RawstronA. Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma: a meta-analysis. JAMA Oncol.3(1), 28–35 (2017).
   PubMed Web of Science ®Google Scholar
• Kumar S , PaivaB, AndersonKCet al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol.17(8), e328–e346 (2016).
   PubMed Web of Science ®Google Scholar
• Einsele H , EngelhardtM, TapprichCet al. Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial. Br. J. Haematol.179(4), 586–597 (2017).
   PubMed Web of Science ®Google Scholar
• Cavo M , TacchettiP, PatriarcaFet al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised Phase 3. Lancet376(9758), 2075–2085 (2010).
   PubMed Web of Science ®Google Scholar