CASSIOPEIA trial: Phase 3 results of daratumumab + bortezomib/thalidomide/dexamethasone in multiple myeloma

The addition of daratumumab to the triplet bortezomib, thalidomide, and dexamethasone (VTd) induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma improved both the depth of response and progression-free survival (PFS) compared with VTd alone [1].

Prof. Phillippe Moreau (University Hospital of Nantes, France) discussed the findings from the randomised, open-label, multicentre, phase 3 CASSIOPEIA trial and the potential role for daratumumab in patients with newly diagnosed multiple myeloma in combination with standard-of-care VTd for patients who are candidates for autologous stem cell transplantation (ASCT).

Patients (n=1,085) were enrolled and randomly assigned to VTd induction and consolidation either with (n=543) or without (n=542) the addition of daratumumab (Dara-VTd) followed by high-dose melphalan and ASCT. The stringent complete response rate was 28.9% with the combination compared with 20.3% in the VTd-alone arm. The median PFS rate at 18 months was 92.7% with daratumumab vs 84.6% without (HR 0.47; 95% CI 0.33-0.67; P<0.0001). Although the data for overall survival is still immature and the median overall survival was not reached in either arm, at 24 months the overall survival rate was 97% with added daratumumab vs 93% without. Death occurred on study in 14 vs 32 patients (HR 0.43; 95% CI 0.23-0.80).

Administering daratumumab in combination with VTd both before and after SCT did not demonstrate additional safety concerns in this setting. The most common grade 3/4 treatment-emergent adverse events noted with the addition of this agent included neutropenia (27.6% with daratumumab vs 14.7% with VTd alone), lymphopenia (17.0% vs 9.7%, respectively), stomatitis (12.7% vs 16.4%), and thrombocytopenia (11.0% vs 7.4%).

In a different session, Prof. Moreau also reported for his colleague Dr Hervé Avet-Loiseau that the minimal residual disease negativity (10−5 sensitivity threshold)., as measured by deep sequencing, was achieved in 64% vs 44% (P<0.0001) [2].

CASSIOPEIA is a 2-part study; the second part of this trial will randomise patients to receive either daratumumab maintenance or no maintenance. The second phase of the trial is currently ongoing, and the researchers expect that a follow-up of at least 1 year is needed.

1. 
   
   1. Moreau P et al. Abstract S145, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.
   2. Avet-Loiseau H, et al. Abstract S874, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.

 



Posted on 9 August 201911 March 2021