The U.S. Food and Drug Administration (FDA) granted breakthrough therapy designation for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of multiple myeloma in patients who have received at least one prior therapy.
The FDA’s decision was based on the results of two phase III studies: CASTOR and POLLUX. The CASTOR trial evaluated daratumumab in combination with bortezomib and dexamethasone compared with bortezomib and dexamethasone alone. Adding daratumumab to treatment resulted in a 61 percent reduction in the risk of disease progression or death (hazard ratio [HR] = 0.39; 95% CI 0.28-0.53; p<0.0001); the median progression-free survival (PFS) was not reached in the daratumumab combination cohort, compared with 7.6 months in the bortezomib and dexamethasone alone cohort. The addition of daratumumab also resulted in an increased overall response rate (ORR): 83 percent versus 63 percent (p<0.0001).
The POLLUX trial evaluated daratumumab in combination with lenalidomide and dexamethasone compared with lenalidomide and dexamethasone. The daratumumab combination therapy resulted in a 63 percent reduction in the risk of disease progression or death compared with lenalidomide and dexamethasone (HR=0.37; 95% CI 0.27-0.52; p<0.0001); the median PFS was not reached in the daratumumab combination cohort compared with 18.4 months for those who received lenalidomide and dexamethasone alone. The addition of daratumumab also significantly increased ORR: 93 percent versus 76 percent (p<0.0001).
Source: FDA news release, July 25, 2016.