Carfilzomib-lenalidomide-dexamethasone vs lenalidomide-dexamethasone in relapsed multiple myeloma by previous treatment
Dimopoulos MA (1), Stewart AK (2), Masszi T (3), Špička I (4), Oriol A (5), Hájek R (6), Rosiñol L (7), Siegel D (8), Mihaylov GG (9), Goranova-Marinova V (10), Rajnics P (11), Suvorov A (12), Niesvizky R (13), Jakubowiak A (14), San-Miguel J (15), Ludwig H (16), Ro S (17), Aggarwal S (17), Moreau P (18), Palumbo A (19)
(1) School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
(2)Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ, USA.
(3) Department of Hematology and Stem-Cell Transplantation, St. István and St. László Hospital, Semmelweis University, Budapest, Hungary.
(4) Department of Internal Medicine, Charles University in Prague, First Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic.
(5) Department of Clinical Hematology, Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol, Institut Josep Carreras, Barcelona, Spain.
(6) Faculty of Medicine, University Hospital Ostrava, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
(7) Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.
(8) Division of Multiple Myeloma, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
(9) Hematological Clinic, Queen Joanna University Hospital, Sofia, Bulgaria.
(10) Hematology Clinic, University Multiprofile Hospital for Active Treatment 'Sv. Georgi' and Medical University, Plovdiv, Bulgaria.
(11) Department of Hematology, Mór Kaposi Teaching Hospital, Kaposvár, Hungary.
(12) First Republican Clinical Hospital of Udmurtia, Izhevsk, Russia.
(13) Multiple Myeloma Center, Weill Cornell Medical College, New York, NY, USA.
(14)Myeloma Program, University of Chicago Medicine, Chicago, IL, USA.
(15) Clinical and Translational Medicine, Clinica Universidad de Navarra-Centro de Investigación Médica Aplicada, IDISNA, CIBERONC, Pamplona, Spain.
(16) Department of Medicine, Wilhelminen Cancer Research Institute, Wilhelminenspital, Vienna, Austria.
(17) Onyx Pharmaceuticals, Inc., An Amgen Subsidiary, South San Francisco, CA, USA.
(18) Department of Hematology, University of Nantes, Nantes, France.
(19) Myeloma Unit, Department of Oncology, University of Turin, Turin, Italy.
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.
CITATION Blood Cancer J. 2017 Apr 21;7(4):e554. doi: 10.1038/bcj.2017.31