POLLUX and CASTOR: Daratumumab Combinations Prolong MRD-Negativity

Therapeutic regimens for multiple myeloma (MM) that use a combination of the anti-CD38 monoclonal antibody daratumumab induce higher rates of sustained minimal residual disease (MRD) negativity compared with standard care, according to results from two clinical trials.

In this study, researchers utilized data from the POLLUX and CASTOR, two ongoing randomized, open-label phase III trials of daratumumab combination regimens for the treatment of relapsed/refractory (RR) MM. They assessed the prognostic value of MRD negative status, as well as rates of sustained negativity.

POLLUX evaluated daratumumab (D) and lenalidomide plus dexamethasone (Rd) in 569 patients who were followed for a median 54.8 months. In CASTOR, daratumumab and bortezomib plus dexamethasone (Vd) was assessed among 498 patients, followed for a median 50.2 months. MRD status was measured at the time of and 3- and 6-months following complete response (CR) in POLLUX, and 6- and 12-months following CR in CASTOR.

Overall rates of MRD negativity were 32.5% for patients who received D-Rd versus 6.7% for Rd alone (P<0.0001); and 15.1% versus 1.6% for D-Vd and Vd, respectively (P<0.0001). In the POLLUX cohort, patients who achieved a CR or better after treatment with daratumumab had higher MRD negativity rates compared with the control, or 57.4% versus 29.2% (P=0.0001). These findings were consistent in CASTOR (52.8% vs. 17.4%; P=0.0035).

Daratumumab combination therapy associated with higher rates of MRD-negative status for six or more months, with 20.3% of the D-Rd group and 10.4% of the D-Vd achieving sustained negativity. Only 2.1% and 1.2% of the respective control groups achieved this. The investigators also found that patients who achieved a CR or better and MRD-negative status had prolonged progression-free survival compared to those who did not.

“Daratumumab-based regimens enabled many patients with RRMM to attain deep and sustained MRD-negative responses, resulting in longer periods without disease progression,” the researchers concluded.

This study was published in the Journal of Clinical Oncology.