Adding daratumumab to treatment with bortezomib, thalidomide, and dexamethasone (VTd) significantly improves survival outcomes in patients with newly diagnosed multiple myeloma, according to research published in The Lancet Oncology.

Long-term results from the phase 3 CASSEOPEIA trial showed that adding daratumumab to VTd induction and consolidation improved progression-free survival (PFS) and overall survival (OS). In addition, patients who received daratumumab maintenance had superior PFS regardless of the induction/consolidation regimen they received.

CASSEOPEIA (NCT02541383) is a 2-part trial that enrolled 1085 patients with newly diagnosed, transplant-eligible multiple myeloma.

In the first part of the trial, patients were randomly assigned to induction and post-transplant consolidation with daratumumab plus VTd (n=543) or VTd only (n=542).

In the second part of the trial, patients who had a partial response or better after completing consolidation were randomly assigned to receive daratumumab maintenance (n=442) or undergo observation (n=444) for 2 years or less.  

At a median follow-up of 80.1 months, the median PFS and OS from first randomization were significantly longer in patients who received daratumumab plus VTd, regardless of whether they received daratumumab as maintenance.

The median PFS from first randomization was 83.7 months in the daratumumab-VTd arm and 52.8 months in the VTd arm (hazard ratio [HR], 0.61, 95% CI; 0.52-0.72; P <.0001).

The median OS from first randomization was not reached in either treatment arm, but the 72-month OS rate was 86.7% in the daratumumab-VTd arm and 77.7% in the VTd arm (HR, 0.55; 95% CI, 0.42-0.73; P <.0001).

At a median follow-up of 70.6 months from second randomization, the median PFS was longer with daratumumab maintenance, regardless of the induction/consolidation regimen patients received.

Overall, the median PFS was not reached in the daratumumab maintenance arm and was 45.8 months in the observation arm (HR, 0.49; 95% CI, 0.40-0.59; P <.0001). The 72-month PFS rates were 57.1% and 36.5% months, respectively.

The median PFS was not reached in patients who received daratumumab-VTd plus daratumumab maintenance and was 72.1 months in those who received daratumumab-VTd plus observation (HR, 0.76; 95% CI, 0.58-1.00; P =.048). The 72-month PFS rates were 60.3% and 50.5%, respectively.

The median PFS was not reached in patients who received VTd induction/consolidation plus daratumumab maintenance and was 32.7 months in those who received VTd induction/consolidation along with observation (HR, 0.34; 95% CI, 0.26-0.44; P <.0001). The 72-month PFS rates were 53.7% and 20.8%, respectively.

OS data from second randomization were immature at the data cutoff. Adverse events were previously reported.

“These findings add to the body of literature (including PERSEUS and GRIFFIN) supporting the use of daratumumab-containing quadruplets as induction and consolidation therapy followed by daratumumab-based maintenance therapy for transplant-eligible patients with newly diagnosed multiple myeloma,” the researchers concluded.

Disclosures: This research was supported by Janssen Research & Development, the Intergroupe Francophone du Myélome, and the Dutch-Belgian Cooperative Trial Group for Hematology Oncology. Some study authors disclosed conflicts of interest. Please see the original reference for complete disclosures.