Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide-dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib-lenalidomide-dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide. Treatment with KRd led to a 12-month improvement in median PFS vs Rd after first relapse (HR 0.713) and a 9-month improvement after ⩾2 previous lines of therapy (HR 0.720). Treatment with KRd led to an approximate 8-month improvement vs Rd in median PFS in bortezomib-exposed patients (HR 0.699), a 15-month improvement in thalidomide-exposed patients (HR 0.587) and a 5-month improvement in lenalidomide-exposed patients (HR 0.796). Objective response and complete response or better rates were higher with KRd vs Rd, irrespective of previous treatment. KRd had a favorable benefit-risk profile and should be considered an appropriate treatment option for patients with 1 or ⩾2 previous lines of therapy and those previously exposed to bortezomib, thalidomide or lenalidomide.

1st Republican Clinical Hospital of Udmurtia Izhevsk Russia

Clinical and Translational Medicine Clinica Universidad de Navarra Centro de Investigación Médica Aplicada IDISNA CIBERONC Pamplona Spain

Department of Clinical Hematology Institut Català d'Oncologia Hospital Universitari Germans Trias i Pujol Institut Josep Carreras Barcelona Spain

Department of Hematology and Stem Cell Transplantation St István and St László Hospital Semmelweis University Budapest Hungary

Department of Hematology Hospital Clínic de Barcelona Barcelona Spain

Department of Hematology Mór Kaposi Teaching Hospital Kaposvár Hungary

Department of Hematology University of Nantes Nantes France

Department of Internal Medicine Charles University Prague 1st Faculty of Medicine and General Teaching Hospital Prague Czech Republic

Department of Medicine Wilhelminen Cancer Research Institute Wilhelminenspital Vienna Austria

Division of Hematology Oncology Mayo Clinic Scottsdale AZ USA

Division of Multiple Myeloma John Theurer Cancer Center at Hackensack University Medical Center Hackensack NJ USA

Faculty of Medicine University Hospital Ostrava Faculty of Medicine University of Ostrava Ostrava Czech Republic

Hematological Clinic Queen Joanna University Hospital Sofia Bulgaria

Hematology Clinic University Multiprofile Hospital for Active Treatment 'Sv Georgi' and Medical University Plovdiv Bulgaria

Multiple Myeloma Center Weill Cornell Medical College New York NY USA

Myeloma Program University of Chicago Medicine Chicago IL USA

Myeloma Unit Department of Oncology University of Turin Turin Italy

Onyx Pharmaceuticals Inc An Amgen Subsidiary South San Francisco CA USA

School of Medicine National and Kapodistrian University of Athens Athens Greece

Zobrazit více v PubMed

Dimopoulos MA, Richardson PG, Moreau P, Anderson KC. Current treatment landscape for relapsed and/or refractory multiple myeloma. Nat Rev Clin Oncol 2015; 12: 42–54. PubMed

Moreau P, San Miguel J, Ludwig H, Schouten H, Mohty M, Dimopoulos M et al. ESMO Guidelines Working Group. multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi133–vi137. PubMed

Song X, Cong Z, Wilson K. Real world treatment patterns and comorbidities and disease-related complications in patients with multiple myeloma in the United States. Curr Med Res Opin 2016; 32: 95–103. PubMed

National Comprehensive Care Network (2016). Clinical Practice Guidelines in Oncology. Multiple Myeloma.

Kumar SK, Therneau TM, Gertz MA, Lacy MQ, Dispenzieri A, Rajkumar SV et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc 2004; 79: 867–874. PubMed

Onyx Pharmaceuticals, Inc. (2016). KYPROLIS® (carfilzomib): Full Prescribing Information (South San Francisco, CA, USA).

Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015; 372: 142–152. PubMed

Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473. PubMed

Bladé J, Samson D, Reece D, Apperley J, Björkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115–1123. PubMed

Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23: 3–9. PubMed PMC

National Cancer Institute (2010). Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Rockville, MD, USA).

San Miguel JF, Weisel KC, Song KW, Delforge M, Karlin L, Goldschmidt H et al. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone vs. high-dose dexamethasone in relapsed/refractory multiple myeloma. Haematologica 2015; 100: 1334–1339. PubMed PMC

Berenson JR, Hilger JD, Yellin O, Dichmann R, Patel-Donnelly D, Boccia RV et al. Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy. Leukemia 2014; 28: 1529–1536. PubMed

Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R et al. Carfilzomib and dexamethasone vs. bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol 2016; 17: 27–38. PubMed

Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood 2012; 120: 2817–2825. PubMed PMC

Siegel D, Martin T, Nooka A, Harvey RD, Vij R, Niesvizky R et al. Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies. Haematologica 2013; 98: 1753–1761. PubMed PMC

Once- versus twice-weekly carfilzomib in relapsed and refractory multiple myeloma by select patient characteristics: phase 3 A.R.R.O.W. study subgroup analysis

Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in the phase III ASPIRE study

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01080391