Carfilzomib in combination with dexamethasone (Kd) is superior to bortezomib plus dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma regardless of cytogenetic risk, according to a study published in the journal Leukemia.1
The phase 3 ENDEAVOR trial (ClinicalTrials.gov Identifier: NCT01568866) demonstrated that carfilzomib plus dexamethasone significantly reduced the risk of progression or death by 47% compared with bortezomib plus dexamethasone in patients with relapsed or refractory multiple myeloma (hazard ratio [HR], 0.53; 95% CI, 0.44-0.65; P < .0001).
In a preplanned subgroup analysis, researchers evaluated efficacy of carfilzomib plus dexamethasone vs bortezomib plus dexamethasone by cytogenetic risk. Of the 785 patients with known cytogenetics in ENDEAVOR, 27% and 73% had high-risk and standard-risk cytogenetics, respectively.
Among patients with high-risk cytogenetics, treatment with carfilzomib was associated with a 35% reduced risk of progression or death compared with bortezomib (HR, 0.65; 95% CI, 0.45-0.92; P =.0075). Median progression-free survival was 8.8 months with the carfilzomib regimen and 6.0 months with bortezomib.
In the standard-risk group, carfilzomib plus dexamethasone significantly reduced the risk of progression or death by 56% vs bortezomib plus dexamethasone (HR, 0.44; 95% CI, 0.33-0.58; P <.0001); median progression-free survival was not estimable and 10.2 months, respectively.
Investigators also found that 72.2% of carfilzomib-treated patients with high-risk cytogenetics achieved an overall response compared with 58.4% of bortezomib-treated patients in the high-risk group. Similarly, 79.2% of those with standard-risk cytogenetics given carfilzomib vs 66.0% of those in the bortezomib group had a response.
Researchers observed complete responses or better in 15.5% of patients with high-risk cytogenetics and 13.0% of those with standard-risk cytogenetics who received carfilzomib. Only 4.4% of high-risk patients and 7.9% of standard-risk patients treated with bortezomib achieved a complete response or better.
1. Chng WJ, Goldschmidt H, Dimopoulos MA, et al. Carfilzomib–dexamethasone vs bortezomib–dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR. Leukemia. 2017 Feb 3. doi: 10.1038/leu.2016.390 [Epub ahead of print]