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 .).
