Philippe Moreau, MD, Hematology Department, University Hospital of Nantes, France, discusses the phase 3 CASSIOPEIA study on daratumumab maintenance plus bortezomib, thalidomide, and dexamethasone (VTd) in patients with newly diagnosed multiple myeloma (MM). These data were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Transcript

Hi, my name is Philippe Moreau. I'm working at the Hematology Department of the University Hospital of Nantes in France.

I was able to present at ASCO 2021 the results of the part 2 of the CASSIOPEIA study. CASSIOPEIA is a randomized phase 3 study in patients with transplant-eligible newly diagnosed multiple myeloma.

We have enrolled 1,085 patients into the study. In the part 1 of the trial, we have shown that the addition of daratumumab to the triplet bortezomib, thalidomide, and dexamethasone, both before and after stem cell transplantation, was able to improve and prolong progression-free survival compared with VTd alone.

These results supported the regulatory approvals for DARA-VTd in transplant-eligible patients with newly diagnosed multiple myeloma.

In the study, patients who were able to reach at least partial response after the first part, induction with VTd or VTd-DARA and stem cell transplantation, were re-randomized in part 2 to receive either daratumumab single-agent IV every 8 weeks at the dose of 16 mg/kg for a fixed duration of 2 years versus no maintenance.

I presented at ASCO the results of this part 2 maintenance with DARA versus no maintenance with a primary endpoint of progression-free survival. 886 patients underwent the second randomization DARA or no DARA. The disease characteristics were well-balanced between groups and the study met its primary endpoint.

We were able to show that daratumumab maintenance is improving progression-free survival significantly, with a hazard ratio of 0.53, with a median follow-up of 3 years. The benefit of daratumumab in terms of PFS was observed across almost all subgroups of patients, with the exception of patients who did receive DARA-VTd induction and consolidation.

It means that daratumumab maintenance is only improving the progression-free survival of patients who did not receive daratumumab upfront. We looked at this interaction between maintenance and the first part of the study, induction consolidation.

PFS was not different for patients who did receive DARA-VTd upfront and daratumumab maintenance versus DARA-VTd upfront and observation, indicating that the PFS benefit was observed only for patients who were treated with VTd upfront. VTd-DARA maintenance was superior to VTd versus observation only during maintenance.

We also looked at the update analysis from the start of the study from first randomization with a median follow-up of almost 4 years. We are clearly confirming the benefit of DARA-VTd induction consolidation versus VTd alone, with significant PFS benefit and already a trend for a better overall survival.

We looked as well at the progression-free survival to PFS2, and there is not yet any difference, but we can see some separation of the PFS2 curves. The best one is the one that is associated with daratumumab induction and also daratumumab maintenance.

To conclude, I would say that the reduced frequency DARA maintenance every 8 weeks significantly improved post-stem cell transplantation outcomes in patients with newly diagnosed myeloma who received VTd induction consolidation. We need, definitely, a longer follow-up to assess potential PFS2 or overall survival benefit.

Thank you for your kind attention.