Clinical trial NCT01080391: Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma
Official title: A Randomized, Multicenter, Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsed Multiple Myeloma
Keywords: Multiple Myeloma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-03-04
Enrollment: 792
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective was to compare progression-free survival in adults with relapsed multiple myeloma who are receiving CRd vs participants receiving Rd in a randomized multicenter setting.

Detailed description: This is a Phase 3, randomized, open-label, multicenter study comparing two treatment regimens for adults with relapsed multiple myeloma. Eligible subjects will be randomized in a 1:1 ratio to receive either the control Rd or CRd. Randomization will be stratified by β2 microglobulin levels (\< vs ≥ 2.5 mg/L), prior bortezomib (no vs yes), and prior lenalidomide (no vs yes). Participants will receive the treatment determined by randomization in 28-day cycles until disease progression or unacceptable toxicity (whichever occurs first).

Eligibility criteria: Inclusion Criteria:

1. Symptomatic multiple myeloma
2. Measurable disease, as defined by one or more of the following (assessed within 21 days prior to randomization):

   * Serum M-protein ≥ 0.5 g/dL
   * Urine Bence-Jones protein ≥ 200 mg/24 hours
   * For immunoglobulin A (IgA) patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL)
3. Prior treatment with at least one, but no more than three, regimens for multiple myeloma
4. Documented relapse or progressive disease on or after any regimen
5. Achieved a response to at least one prior regimen
6. Age ≥ 18 years
7. Life expectancy ≥ 3 months
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
9. Adequate hepatic function, with serum alanine aminotransferase (ALT) ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 21 days prior to randomization
10. Absolute neutrophil count ≥ 1.0 × 10\^9/L within 21 days prior to randomization
11. Hemoglobin ≥ 8 g/dL (80 g/L) within 21 days prior to randomization
12. Platelet count ≥ 50 × 10\^9/L (≥ 30 × 10\^9/L if myeloma involvement in the bone marrow is \> 50%) within 21 days prior to randomization
13. Creatinine clearance (CrCl) ≥ 50 mL/minute within 21 days prior to randomization
14. Written informed consent in accordance with federal, local, and institutional guidelines
15. Females of childbearing potential must agree to ongoing pregnancy testing and to practice contraception
16. Male subjects must agree to practice contraception

Exclusion Criteria:

1. If previously treated with bortezomib (alone or in combination), progression during treatment
2. If previously treated with a lenalidomide and dexamethasone (len/dex) combination:

   * Progression during the first 3 months of initiating treatment
   * Any progression during treatment if the len/dex combination was the subject's most recent line of therapy
3. Discontinuation of previous lenalidomide or dexamethasone due to intolerance; subjects intolerant to bortezomib are not excluded
4. Prior carfilzomib treatment
5. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
6. Waldenström's macroglobulinemia or IgM myeloma
7. Plasma cell leukemia (\> 2.0 × 10\^9/L circulating plasma cells by standard differential)
8. Chemotherapy or investigational agent within 3 weeks prior to randomization or antibody therapy within 6 weeks prior to randomization
9. Radiotherapy to multiple sites or immunotherapy/antibody therapy within 28 days prior to randomization; localized radiotherapy to a single site within 7 days prior to randomization
10. Corticosteroid therapy at a dose equivalent to dexamethasone \> 4 mg/day within 21 days prior to randomization
11. Pregnant or lactating females
12. Major surgery within 21 days prior to randomization
13. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization
14. Known human immunodeficiency virus infection
15. Active hepatitis B or C infection
16. Myocardial infarction within 4 months prior to randomization, New York Hear Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
17. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomization
18. Other malignancy, including myelodysplastic syndromes (MDS), within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
19. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to randomization
20. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
21. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
22. Ongoing graft-vs-host disease
23. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization
24. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization through the data cutoff date of 16 June 2014. Median follow-up time was approximately 31 months.
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization through the data cutoff date of 28 April 2017 for the final analysis of overall survival; median follow up time was 67.1 months in each treatment group.
measure: Overall Response Rate
timeFrame: From randomization through the data cutoff date of 16 June 2014. Median follow-up time was approximately 31 months.
measure: Disease Control Rate
timeFrame: From randomization through the data cutoff date of 16 June 2014. Median follow-up time was approximately 31 months.
measure: Duration of Response
timeFrame: From randomization through the data cutoff date of 16 June 2014. Longest follow-up time was approximately 42 months.
measure: Duration of Disease Control
timeFrame: From randomization through the data cutoff date of 16 June 2014. Longest follow-up time was approximately 46 months.
measure: Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores
timeFrame: Cycle 1 Day 1 (Baseline), Day 1 of Cycles 3, 6, 12, 18
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Burbank
country: United States
facility: Providence St. Joseph Medical Center
state: California
city: Santa Rosa
country: United States
facility: St. Jude Hospital Yorba Linda dba; St. Joseph Heritage Healthcare
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Lecanto
country: United States
facility: Cancer and Blood Disease Center
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Ann Arbor
country: United States
facility: The University of Michigan - Comprehensive Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU Clinical Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Chattanooga
country: United States
facility: Associates in Oncology and Hematology
state: Tennessee
city: Amarillo
country: United States
facility: The Don & Sybil Harrington Cancer Center
state: Texas
city: Dallas
country: United States
facility: Baylor Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: The University of Texas, MD Anderson Cancer Center
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin
state: Wisconsin
city: Wien
country: Austria
facility: Medizinische Universitat Wien
city: Wien
country: Austria
facility: Wilhelminspital der Stadt Wien, Zentrum fur Onkologie und Hamatologie
city: Antwerpen
country: Belgium
facility: Ziekenhuisnetwerk Antwerpen - AZ Stuivenberg
city: Brugge
country: Belgium
facility: AZ Sint-Jan AV
city: Brussels
country: Belgium
facility: UZ Brussel
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment, "Dr. Georgi Stranski"
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Georgi"
city: Sofia
country: Bulgaria
facility: Military Medical Academy Multiprofile Hospital for Active Treatment
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematological Diseases
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Sveta Marina"
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta, Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: St John's
country: Canada
facility: General Hospital, Health Sciences Centre
state: Newfoundland and Labrador
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center, Royal Victoria Hospital
state: Quebec
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis - Jewish General Hospital
state: Quebec
city: Brno
country: Czechia
facility: University Hospital Brno, Department of Internal Medicine - Hematooncology
city: Hradec Kralove
country: Czechia
facility: University Hospital Hradec Kralove
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Praha 10
country: Czechia
facility: University Hospital Kralovske Vinohrady - Prague
city: Praha 2
country: Czechia
facility: General University Hospital Prague
city: Clamart
country: France
facility: Hospital Antoine Beclere
city: Le Mans
country: France
facility: Clinique Victor Hugo - Centre Jean Bernard
city: Lille
country: France
facility: Hopital Claude Huriez
city: Mulhouse
country: France
facility: CH de Mulhouse, Hopital Emile Muller
city: Nantes
country: France
facility: CHU Nantes Hotel Dieu
city: Paris
country: France
facility: Hopital Saint-Antoine
city: Paris
country: France
facility: Groupe Hospitalier Necker - Enfants Malades
city: Toulouse
country: France
facility: Cancer Institut Universitaire de Toulouse-Oncopole (iUCT)
city: Vandoeuvre-Les-Nancy
country: France
facility: Hopitaux de Brabois
city: Dusseldorf
country: Germany
facility: University of Dusseldorf
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nordwest
city: Hamburg
country: Germany
facility: University of Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: Universitat Heidelberg
city: Koblenz
country: Germany
facility: Stiftungsklinikum Mittelrhein
city: Munchen
country: Germany
facility: LMU Klinikum der Universitat
city: Munster
country: Germany
facility: Universitatsklinikum Munster
city: Wurzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Athens
country: Greece
facility: Alexandra Hospital
city: Patras
country: Greece
facility: University General Hospital of Patras
city: Budapest
country: Hungary
facility: St. Istvan and St. Laszlo Hospital of Budapest
city: Debrecen
country: Hungary
facility: University of Debrecen, Medical and Health Science Center
city: Gyor
country: Hungary
facility: Petz Aladar County Teaching Hospital
city: Gyula
country: Hungary
facility: Bekes County Pandy Kalman Hospital
city: Kaposvar
country: Hungary
facility: Kaposi Mor County Teaching Hospital
city: Pecs
country: Hungary
facility: University of Pecs
city: Szeged
country: Hungary
facility: University of Szeged, Albert Szent-Gyorgi Clinical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center, Ein Kerem
city: Nahariya
country: Israel
facility: Western Gailee Hospital - Nahariya
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Milano
country: Italy
facility: Azienda Ospedallera Niguarda Ca Granda
city: Novara
country: Italy
facility: Azienda Ospedllero Maggiore della Carita
city: Pisa
country: Italy
facility: Azienda Ospedaliera Pisana Ospendale Santa Chiara - Main
city: Roma
country: Italy
facility: Ospedale S. Eugenio
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza di Torino
city: Rotterdam
country: Netherlands
facility: Erasmus MC, Department of Haematology
city: Gdansk
country: Poland
facility: University Clinical Centre, Department of Hematologii Transplantologii
city: Gorzow Wielkopolski
country: Poland
facility: Samodzielny Publ. Szp. Wojewodzki w Gorzow Wlkp.
city: Katowice
country: Poland
facility: Independent Public Teaching Hospital of Medical University of Silesia in Katowice
city: Lodz
country: Poland
facility: Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz
city: Suwalki
country: Poland
facility: Szpital Wojewwodzki im. dr Ludwika Rydygiera w Suwalkach
city: Torun
country: Poland
facility: Nicolaus Copernicus Municipal Specialist Hospital
city: Warszawa
country: Poland
facility: Maria Sklodowska-Curie Institute of Oncology
city: Zamosc
country: Poland
facility: Zamojski Non-Public Hospital
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute, "Stefan Berceanu" Center for Hematology and Bone Marrow Transplantation
city: Bucharest
country: Romania
facility: Coltea Clinical Hospital
city: Bucharest
country: Romania
facility: Bucharest University Emergency Hospital
city: Iasi
country: Romania
facility: Regional Institute of Iasi
city: Syktyvkar
country: Russian Federation
facility: State Medical Institution Komi Republican Oncological Center
state: Komi Republic
city: Izhevsk
country: Russian Federation
facility: First Republican Clinical Hospital under the Ministry of Healthcare of the Republic of Udmurtia
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Scientific Institution: N.N. Blokhin Russian Cancer Research Center
city: Moscow
country: Russian Federation
facility: Moscow State Medical Institution Municipal City Clinical Hospital n.a. S.P. Botkin
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution: Hematology Research Center under MoH
city: St. Petersburg
country: Russian Federation
facility: FSBI: Russian Research Institute of Hematology and Blood Transfusion under the Ferderal Agency for M&B
city: St. Petersburg
country: Russian Federation
facility: State Higher Educational Institution: St Petersburg State Medical University n.a.I.P Pavlov
city: St. Petersburg
country: Russian Federation
facility: SHEI: First St. Petersburg State Medical University N.a.I.P Pavlov under MoH, Clinic of Bone Marrow Transplant
city: St. Petersburg
country: Russian Federation
facility: Federal State Budget Institute: Federal Almalov Medical Research Centre under Ministry of Healthcare
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia, Clinic of Hematology
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
city: Belgrade
country: Serbia
facility: Military Medical Academy, Clinic of Hematology
city: Nis
country: Serbia
facility: Clinical Center Nis, Clinic of Hematology
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina, Clinic of Hematology
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: San Sebastian
country: Spain
facility: Hospital Donostia
city: Valencia
country: Spain
facility: Hospital Universitario y Politeecnico La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Stockholm
country: Sweden
facility: Karolinska Universitetsjukhuset i Huddinge
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna, Hematologiskt Centrum
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital
city: London
country: United Kingdom
facility: Royal Free Hampstead
city: London
country: United Kingdom
facility: St. Georges Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals (City Campus)
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton Hospital NHS Trust
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Dimopoulos M, Wang M, Maisnar V, Minarik J, Bensinger W, Mateos MV, Obreja M, Blaedel J, Moreau P. 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. J Hematol Oncol. 2018 Apr 4;11(1):49. doi: 10.1186/s13045-018-0583-7.
citation: Avet-Loiseau H, Fonseca R, Siegel D, Dimopoulos MA, Spicka I, Masszi T, Hajek R, Rosinol L, Goranova-Marinova V, Mihaylov G, Maisnar V, Mateos MV, Wang M, Niesvizky R, Oriol A, Jakubowiak A, Minarik J, Palumbo A, Bensinger W, Kukreti V, Ben-Yehuda D, Stewart AK, Obreja M, Moreau P. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma. Blood. 2016 Sep 1;128(9):1174-80. doi: 10.1182/blood-2016-03-707596. Epub 2016 Jul 20.
citation: Dimopoulos MA, Stewart AK, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel D, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak A, San-Miguel J, Ludwig H, Ro S, Aggarwal S, Moreau P, Palumbo A. Carfilzomib-lenalidomide-dexamethasone vs lenalidomide-dexamethasone in relapsed multiple myeloma by previous treatment. Blood Cancer J. 2017 Apr 21;7(4):e554. doi: 10.1038/bcj.2017.31.
citation: Dimopoulos MA, Stewart AK, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel D, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak A, San-Miguel J, Ludwig H, Palumbo A, Obreja M, Aggarwal S, Moreau P. 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. doi: 10.1111/bjh.14549. Epub 2017 Feb 17.
citation: Jakubowiak AJ, Campioni M, Benedict A, Houisse I, Tichy E, Giannopoulou A, Aggarwal SK, Barber BL, Panjabi S. Cost-effectiveness of adding carfilzomib to lenalidomide and dexamethasone in relapsed multiple myeloma from a US perspective. J Med Econ. 2016 Nov;19(11):1061-1074. doi: 10.1080/13696998.2016.1194278. Epub 2016 Jun 16.
citation: Stewart AK, Dimopoulos MA, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel DS, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Buchanan J, Cocks K, Yang X, Xing B, Zojwalla N, Tonda M, Moreau P, Palumbo A. Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma. J Clin Oncol. 2016 Nov 10;34(32):3921-3930. doi: 10.1200/JCO.2016.66.9648.
citation: Chari A, Stewart AK, Russell SD, Moreau P, Herrmann J, Banchs J, Hajek R, Groarke J, Lyon AR, Batty GN, Ro S, Huang M, Iskander KS, Lenihan D. Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. Blood Adv. 2018 Jul 10;2(13):1633-1644. doi: 10.1182/bloodadvances.2017015545.
citation: Facon T, Niesvizky R, Mateos MV, Siegel D, Rosenbaum C, Bringhen S, Weisel K, Ho PJ, Ludwig H, Kumar S, Wang K, Obreja M, Yang Z, Klippel Z, Mezzi K, Goldrick A, Tekle C, Dimopoulos MA. Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma. Blood Adv. 2020 Nov 10;4(21):5449-5459. doi: 10.1182/bloodadvances.2020001965.
citation: Hari P, Mateos MV, Abonour R, Knop S, Bensinger W, Ludwig H, Song K, Hajek R, Moreau P, Siegel DS, Feng S, Obreja M, Aggarwal SK, Iskander K, Goldschmidt H. Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes. Leukemia. 2017 Dec;31(12):2630-2641. doi: 10.1038/leu.2017.122. Epub 2017 Apr 25.
citation: Leleu X, Martin TG, Einsele H, Lyons RM, Durie BGM, Iskander KS, Ailawadhi S. Role of Proteasome Inhibitors in Relapsed and/or Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2019 Jan;19(1):9-22. doi: 10.1016/j.clml.2018.08.016. Epub 2018 Sep 5.
citation: Mateos MV, Goldschmidt H, San-Miguel J, Mikhael J, DeCosta L, Zhou L, Obreja M, Blaedel J, Szabo Z, Leleu X. Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trials. Hematol Oncol. 2018 Apr;36(2):463-470. doi: 10.1002/hon.2499. Epub 2018 Feb 15.
citation: Siegel DS, Dimopoulos MA, Ludwig H, Facon T, Goldschmidt H, Jakubowiak A, San-Miguel J, Obreja M, Blaedel J, Stewart AK. Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. J Clin Oncol. 2018 Mar 10;36(8):728-734. doi: 10.1200/JCO.2017.76.5032. Epub 2018 Jan 17.
citation: Weisel K, Mateos MV, Gay F, Delforge M, Cook G, Szabo Z, Desgraz R, DeCosta L, Moreau P. Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR. Leukemia. 2021 Jun;35(6):1732-1744. doi: 10.1038/s41375-020-01049-5. Epub 2020 Oct 16.
citation: Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel DS, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Wang M, Maisnar V, Minarik J, Bensinger WI, Mateos MV, Ben-Yehuda D, Kukreti V, Zojwalla N, Tonda ME, Yang X, Xing B, Moreau P, Palumbo A; ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015 Jan 8;372(2):142-52. doi: 10.1056/NEJMoa1411321. Epub 2014 Dec 6.