PMID- 29341834
OWN - NLM
STAT- MEDLINE
DCOM- 20190717
LR  - 20220331
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 36
IP  - 8
DP  - 2018 Mar 10
TI  - Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone 
      in Patients With Relapsed or Refractory Multiple Myeloma.
PG  - 728-734
LID - 10.1200/JCO.2017.76.5032 [doi]
AB  - Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) 
      versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or 
      refractory multiple myeloma, progression-free survival was significantly improved 
      in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This 
      prespecified analysis reports final overall survival (OS) data and updated safety 
      results. Patients and Methods Adults with relapsed multiple myeloma (one to three 
      prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio 
      to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease 
      progression, or occurrence of unacceptable toxicity. After 18 cycles, all 
      patients received Rd only. Progression-free survival was the primary end point; 
      OS was a key secondary end point. OS was compared between treatment arms using a 
      stratified log-rank test. Results Median OS was 48.3 months (95% CI, 42.4 to 52.8 
      months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard 
      ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving 
      one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it 
      was 6.5 months longer for KRd versus Rd among patients receiving >/= two prior 
      lines of therapy. Rates of treatment discontinuation because of adverse events 
      (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade >/= 3 AE rates were 87.0% (KRd) and 
      83.3% (Rd). Selected grade >/= 3 AEs of interest (grouped terms; KRd v Rd) included 
      acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%), ischemic heart 
      disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic thrombocytopenia 
      (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%). Conclusion KRd 
      demonstrated a statistically significant and clinically meaningful reduction in 
      the risk of death versus Rd, improving survival by 7.9 months. The KRd efficacy 
      advantage is most pronounced at first relapse.
FAU - Siegel, David S
AU  - Siegel DS
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
FAU - Dimopoulos, Meletios A
AU  - Dimopoulos MA
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
FAU - Ludwig, Heinz
AU  - Ludwig H
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
FAU - Facon, Thierry
AU  - Facon T
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
FAU - Goldschmidt, Hartmut
AU  - Goldschmidt H
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
FAU - Jakubowiak, Andrzej
AU  - Jakubowiak A
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
FAU - San-Miguel, Jesus
AU  - San-Miguel J
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
FAU - Obreja, Mihaela
AU  - Obreja M
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
FAU - Blaedel, Julie
AU  - Blaedel J
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
FAU - Stewart, A Keith
AU  - Stewart AK
AD  - David S. Siegel, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian 
      University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research 
      Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hopital Claude 
      Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille, France; 
      Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor 
      Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago 
      Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de 
      Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, 
      Centro de Investigacion Biomedica en Red de Cancer, Pamplona, Spain; Mihaela 
      Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo 
      Clinic, Scottsdale, AZ.
LA  - eng
SI  - ClinicalTrials.gov/NCT01080391
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180117
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Oligopeptides)
RN  - 72X6E3J5AR (carfilzomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Dexamethasone/pharmacology/*therapeutic use
MH  - Female
MH  - Humans
MH  - Lenalidomide/pharmacology/*therapeutic use
MH  - Male
MH  - Multiple Myeloma/*drug therapy/mortality/pathology
MH  - Neoplasm Recurrence, Local
MH  - Oligopeptides/pharmacology/*therapeutic use
MH  - Survival Analysis
EDAT- 2018/01/18 06:00
MHDA- 2019/07/18 06:00
CRDT- 2018/01/18 06:00
PHST- 2018/01/18 06:00 [pubmed]
PHST- 2019/07/18 06:00 [medline]
PHST- 2018/01/18 06:00 [entrez]
AID - 10.1200/JCO.2017.76.5032 [doi]
PST - ppublish
SO  - J Clin Oncol. 2018 Mar 10;36(8):728-734. doi: 10.1200/JCO.2017.76.5032. Epub 2018 
      Jan 17.