Targeted treatments for multiple myeloma: specific role of carfilzomib

Figures & data

Table 1 Key completed studies evaluating carfilzomib in MM

Study	Population	Patients	ORR (%)	CR + VGPR	PFS (months)	OS (months)
PX-171-001 (Phase I) carfilzomib (single agent)^Citation13	Hematologic malignancies (MM, NHL, WM, HL)	29	NR	NR	NR	NR
PX-171-002 (Phase I) carfilzomib (single agent)^Citation12	Hematologic malignancies (MM, NHL, HL)	48	NR	NR	NR	NR
PX-171-003-A0 (Phase IIB) carfilzomib (single agent)^Citation35	RRMM	46	16.7	0 (0 + 0)	3.5	NR
PX-171-003-A1 (Phase II) carfilzomib (single agent)^Citation15	RRMM	266	23.7	5.5% (0.4% + 5.1%)	3.7	15.6
PX-171-004 (Phase II) carfilzomib (single agent, 20 mg/m^2 versus 27 mg/m^2)^Citation17	RRMM	129	42.4 versus 52.2	17% (3.4% + 13.6%) versus 28.4% (1.5% + 26.9%)	8.2 versus NR	NR
PX-171-005 (Phase II) carfilzomib (single agent)^Citation33	RRMM: renal dysfunction	50	25.5	0 (0 + 0)	NR	NR
PX-171-006 (Phase IB) carfilzomib + Rd^Citation22	Relapsed or progressive MM	40	62.5	35% (2.5% + 32.5%)	10.2	NR
PX-171-006 (Phase II) carfilzomib + Rd^Citation21	Relapsed or progressive MM	52	76.9	42.2% (5.7% + 36.5%)	28.7	37
PX-171-007 (Phase IB/II) carfilzomib (single agent) dose-expansion cohort^Citation16	Relapsed MM, solid tumors or lymphoma	33	55	28% (5% + 23%)	7	NR
Carfilzomib + Rd (Phase I/II)^Citation26	Newly diagnosed	53	98	81% (62% + 19%)	NR	NR
Carfilzomib + clarithromycin + Rd (Phase I)^Citation27	Newly diagnosed	24	87	61% (13% + 48%)	NR	NR
FOCUS: PX-171-011 (Phase III) carfilzomib versus best supportive care^Citation18	RRMM	315	NR	NR	NR	NR
ASPIRE: PX-171-009 (Phase III) carfilzomib + lenalidomide + dexamethasone versus lenalidomide + dexamethasone Planned interim analysis^Citation25	Relapsed MM	792	NR	NR	26.3 versus 17.6	NR

Abbreviations: ORR, overall response rate; CR, complete response; VGPR, very good partial response; PFS, progression-free survival; OS, overall survival; RRMM, relapsed and refractory multiple myeloma; NHL, non-Hodgkin’s lymphoma; WM, Waldenström’s macroglobulinemia; Rd, Revlimid and dexamethasone; NR, not reported.

Table 2 Key ongoing trials in newly diagnosed multiple myeloma (MM)

Regimen	Population	Authors	Patients	Phase
Carfilzomib + bendamustine + dexamethasone	Newly diagnosed	Lentzsch et al^Citation49	34	I/IIB
Carfilzomib + high-dose melphalan	Transplant-eligible (preparative regimen)	Costa et al^Citation50	58	I/IIA
Carfilzomib + melphalan + prednisone versus bortezomib + melphalan + prednisone (CLARION)	Transplant-ineligible, newly diagnosed	Facon et al^Citation48	882	III
Initial and posttransplant treatment with carfilzomib + revlimid + dexamethasone	Newly diagnosed, transplant-eligible, pre- and post-ASCT	Jakubowiak et al^Citation51	44	II
Carfilzomib + lenalidomide + dexamethasone	Smoldering MM (high risk)	Landgren et al^Citation52	30	II

Abbreviation: ASCT, autologous stem cell transplantation.

Table 3 Key ongoing trials in relapsed or refractory multiple myeloma

Regimen	Population	Author(s)	Patients	Phase
High-dose carfilzomib for MM patients with progression on standard dose carfilzomib	RRMM	Chari et al^Citation53	36	II
Bruton’s tyrosine-kinase inhibitor + carfilzomib in RRMM	RRMM	Pharmacyclics^Citation54	223	I/IIB
Arry-520 + carfilzomib	RRMM	Shah et al^Citation55	76	I/II
Two dose levels of carfilzomib + dexamethasone for RRMM (S1304)	RRMM	Ailawadhi et al^Citation56	140	II
Panobinostat + carfilzomib	RRMM	Kaufman et al^Citation57	36	I
Pomalidomide + dexamethasone + carfilzomib (PdC)	RRMM	Jakubowiak et al^Citation58	92	IB/II
Carfilzomib + lenalidomide + vorinostat + dexamethasone	RRMM	Siegel et al^Citation59	50	I/II
Carfilzomib + pegylated liposomal doxorubicin + dexamethasone	RRMM	Vij et al^Citation60	53	I/II
60-Minute infusion of carfilzomib	RRMM	Berenson et al^Citation61	38	I/II
Carfilzomib/SAHA + high-dose gemcitabine/busulfan/melphalan + ASCT	RRMM	Nieto^Citation62	75	II

Abbreviations: RRMM, relapsed and refractory multiple myeloma; MM, multiple myeloma; SAHA, suberoylanilide hydroxamic acid; ASCT, autologous stem cell transplantation.

O’ConnorOAA phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignanciesClin Cancer Res200915227085709119903785

 PubMed Web of Science ®Google Scholar

AlsinaMA 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 lymphomaClin Cancer Res201218174830484022761464

 PubMed Web of Science ®Google Scholar

JagannathSAn 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 myelomaClin Lymphoma Myeloma Leuk201212531031823040437

 PubMed Web of Science ®Google Scholar

SiegelDSA phase 2 study of single-agent carfilzomib (PX-171–003-A1) in patients with relapsed and refractory multiple myeloma201212028172825

 Google Scholar

VijRAn open-label, single-arm, phase 2 (PX-171–004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myelomaBlood2012119245661567022555973

 PubMed Web of Science ®Google Scholar

BadrosAZCarfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safetyLeukemia20132781707171423364621

 PubMed Web of Science ®Google Scholar

NiesvizkyRPhase Ib dose-escalation study (PX-171–006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myelomaClin Cancer Res20131982248225623447001

 PubMed Web of Science ®Google Scholar

WangMPhase 2 dose-expansion study (PX-171–006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myelomaBlood2013122183122312824014245

 PubMed Web of Science ®Google Scholar

PapadopoulosKPPhase 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 MyelomaJ Clin Oncol2014

 Google Scholar

JakubowiakAJTreatment outcome with the combination of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) for newly diagnosed multiple myeloma (NDMM) after extended follow-upASCO Meeting Abstracts20133115_suppl8543

 Google Scholar

AllanJNCar-Bird [Carfilzomib, Clarithromycin(Biaxin(R)), Lenalidomide/(Revlimid(R)), Dexamethasone) For Newly-Diagnosed Multiple Myeloma201312232163216

 Google Scholar

Amgen Announces Top-Line Results From Phase 3 Focus Trial Of Kyprolis® In Patients With Relapsed And Advanced Refractory Multiple Myeloma8122014 Available from: http://www.amgen.com

 Google Scholar

AmgenAmgen Announces Phase 3 ASPIRE Trial of Kyprolis In Patients With Relapsed Multiple Myeloma Met Primary Endpoint842014 Available from: http://www.amgen.com

 Google Scholar

Columbia University. ClinicalTrials.govCarfilzomib With Benda-mustine and Dexamethasone in Multiple Myeloma Available from: http://clinicaltrials.gov/ct2/show/NCT02002598. NLM identifier: NCT02002598Accessed: August 10, 2014

 Google Scholar

Medical University of South Carolina. ClinicalTrials.govCarfilzomib + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation Available from: http://clinicaltrials.gov/ct2/show/NCT01690143. NLM identifier: NCT01690143Accessed: August 10, 2014

 Google Scholar

Onyx Pharmaceuticals. ClinicalTrials.govPhase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma (CLARION) Available from: http://clinicaltrials.gov/show/NCT01818752. NLM identifier: NCT01818752Accessed: August 10, 2014

 Google Scholar

University of Chicago. ClinicalTrials.govCarfilzomib, Lenalidomide, and Dexamethasone Before and After Stem Cell Transplant in Treating Patients With Newly Diagnosed Multiple Myeloma Available from: http://clinicaltrials.gov/ct2/show/NCT01816971. NLM identifier: NCT01816971Accessed: August 10, 2014

 Google Scholar

National Cancer Institute. ClinicalTrials.govCarfilzomib, Lenalidomide, and Dexamethasone for Smoldering Multiple Myeloma Available from: http://clinicaltrials.gov/show/NCT01572480. NLM identifier: NCT01572480Accessed: August 10, 2014

 Google Scholar

Onyx Pharmaceuticals. ClinicalTrials.govStudy of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib Available from: http://clinicaltrials.gov/ct2/show/NCT01775553. NLM identifier: NCT01775553Accessed: August 10, 2014

 Google Scholar

Pharmacyclics. ClinicalTrials.govStudy of the Bruton’s Tyrosine Kinase Inhibitor in Combination With Carfilzomib (Kyprolis™), in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma Available from: http://clinicaltrials.gov/ct2/show/NCT01962792. NLM identifier: NCT01962792Accessed: August 10, 2014

 Google Scholar

M.D. Anderson Cancer Center. ClinicalTrials.govArry-520 + Carfilzomib for Multiple Myeloma (MM) Available from: http://clinicaltrials.gov/ct2/show/NCT01372540. NLM identifier: NCT01372540Accessed: August 10, 2014

 Google Scholar

Southwest Oncology Group. ClinicalTrials.govS1304, Testing Two Doses of Carfilzomib With Dexamethasone for Relapsed or Refractory Myeloma Available from: http://clinicaltrials.gov/ct2/show/NCT01903811. NLM identifier: NCT01903811Accessed: August 10, 2014

 Google Scholar

Emory University. ClinicalTrials.govA Phase I Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed and/or Refractory Multiple Myeloma Available from: http://clinicaltrials.gov/ct2/show/NCT01549431. NLM identifier: NCT01549431Accessed: August 10, 2014

 Google Scholar

University of Chicago. ClinicalTrials.govCarfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma Available from: http://clinicaltrials.gov/ct2/show/NCT01665794. NLM identifier: NCT01665794Accessed: August 10, 2014

 Google Scholar

Hackensack University Medical Center. ClinicalTrials.govA Study of Carfilzomib, Lenalidomide, Vorinostat, and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma (QUAD) Available from: http://clinicaltrials.gov/ct2/show/NCT01297764. NLM identifier: NCT01297764Accessed: August 10, 2014

 Google Scholar

Washington University School of Medicine. ClinicalTrials.govCarfilzomib, Pegylated Liposomal Doxorubicin Hydrochloride, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma Available from: http://clinicaltrials.gov/ct2/show/NCT01246063. NLM identifier: NCT01246063Accessed: August 10, 2014

 Google Scholar

Oncotherapeutics. ClinicalTrials.govSafety, Efficacy, and Pharmacodynamics of a 60-Minute Infusion of Carfilzomib for Progressive Multiple Myeloma Available from: http://clinicaltrials.gov/ct2/show/NCT01792102. NLM identifier: NCT01792102Accessed: August 10, 2014

 Google Scholar

M.D. Anderson Cancer Center. ClinicalTrials.govCarfilzomib/SAHA Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant in Myeloma Available from: http://clinicaltrials.gov/show/NCT02114502. NLM identifier: NCT02114502Accessed: August 10, 2014

 Google Scholar