Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma

ASPIRE Investigators

Research output: Contribution to journalArticle

577 Citations (Scopus)

Abstract

Background Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. Methods We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Results Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P = 0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P = 0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. Conclusions In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.)

Original languageEnglish (US)
Pages (from-to)142-152
Number of pages11
JournalNew England Journal of Medicine
Volume372
Issue number2
DOIs
StatePublished - Jan 8 2015

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Multiple Myeloma
Dexamethasone
Control Groups
Disease-Free Survival
Confidence Intervals
carfilzomib
lenalidomide
Proteasome Inhibitors
Survival Rate
Quality of Life
Survival
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. / ASPIRE Investigators.

In: New England Journal of Medicine, Vol. 372, No. 2, 08.01.2015, p. 142-152.

Research output: Contribution to journalArticle

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title = "Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma",
abstract = "Background Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. Methods We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Results Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95{\%} confidence interval [CI], 0.57 to 0.83; P = 0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3{\%} and 65.0{\%} in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95{\%} CI, 0.63 to 0.99; P = 0.04). The rates of overall response (partial response or better) were 87.1{\%} and 66.7{\%} in the carfilzomib and control groups, respectively (P<0.001; 31.8{\%} and 9.3{\%} of patients in the respective groups had a complete response or better; 14.1{\%} and 4.3{\%} had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7{\%} and 80.7{\%} of patients in the carfilzomib and control groups, respectively; 15.3{\%} and 17.7{\%} of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. Conclusions In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.)",
author = "{ASPIRE Investigators} and Stewart, {Alexander Keith} and Rajkumar, {S Vincent} and Dimopoulos, {Meletios A.} and Tamas Masszi and Ivan Špicka and Albert Oriol and Roman Hajek and Laura Rosinol and Siegel, {David S.} and Mihaylov, {Georgi G.} and Vesselina Goranova-Marinova and Peter Rajnics and Aleksandr Suvorov and Ruben Niesvizky and Jakubowiak, {Andrzej J.} and San-Miguel, {Jesus F.} and Heinz Ludwig and Michael Wang and Vladimir Maisnar and Jiri Minarik and Bensinger, {William I.} and Mateos, {Maria Victoria} and Dina Ben-Yehuda and Vishal Kukreti and Naseem Zojwalla and Tonda, {Margaret E.} and Xinqun Yang and Biao Xing and Philippe Moreau and Antonio Palumbo",
year = "2015",
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T1 - Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma

AU - ASPIRE Investigators

AU - Stewart, Alexander Keith

AU - Rajkumar, S Vincent

AU - Dimopoulos, Meletios A.

AU - Masszi, Tamas

AU - Špicka, Ivan

AU - Oriol, Albert

AU - Hajek, Roman

AU - Rosinol, Laura

AU - Siegel, David S.

AU - Mihaylov, Georgi G.

AU - Goranova-Marinova, Vesselina

AU - Rajnics, Peter

AU - Suvorov, Aleksandr

AU - Niesvizky, Ruben

AU - Jakubowiak, Andrzej J.

AU - San-Miguel, Jesus F.

AU - Ludwig, Heinz

AU - Wang, Michael

AU - Maisnar, Vladimir

AU - Minarik, Jiri

AU - Bensinger, William I.

AU - Mateos, Maria Victoria

AU - Ben-Yehuda, Dina

AU - Kukreti, Vishal

AU - Zojwalla, Naseem

AU - Tonda, Margaret E.

AU - Yang, Xinqun

AU - Xing, Biao

AU - Moreau, Philippe

AU - Palumbo, Antonio

PY - 2015/1/8

Y1 - 2015/1/8

N2 - Background Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. Methods We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Results Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P = 0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P = 0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. Conclusions In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.)

AB - Background Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. Methods We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Results Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P = 0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P = 0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. Conclusions In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.)

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U2 - 10.1056/NEJMoa1411321

DO - 10.1056/NEJMoa1411321

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VL - 372

SP - 142

EP - 152

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 1533-4406

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