1. Daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) as induction and consolidation therapy led to superior progression-free survival and higher MRD-negativity rates compared to VTd alone.
2. Daratumumab maintenance therapy further improved progression-free survival and sustained MRD-negativity rates in patients who had received D-VTd or VTd induction and consolidation therapy.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The present study is a phase 3 randomized controlled trial assessing the long-term impact of daratumumab induction, consolidation and maintenance therapy in patients with newly diagnosed multiple myeloma. Patients aged 18-65 with newly diagnosed, transplant-eligible multiple myeloma were recruited. In Part 1, they were randomly assigned to receive either D-VTd or VTd alone as induction and consolidation therapy. Results from Part 1 demonstrated that the D-VTd group achieved higher rates of complete response, minimal residual disease (MRD) negativity, and prolonged progression-free survival. In Part 2, patients were re-randomized to receive either daratumumab maintenance therapy or observation for up to two years, with daratumumab maintenance significantly improving progression-free survival compared to observation. Strengths of this study include its randomized controlled design and long follow-up period, providing robust and comprehensive data on the long-term benefits of daratumumab in multiple myeloma treatment. Limitations involve the lack of diversity in the study population, as it was conducted exclusively in European countries without collecting data on race and ethnicity. To conclude, the CASSIOPEIA study demonstrated that adding daratumumab to both induction and maintenance therapy significantly improved progression-free survival and minimal residual disease negativity rates in transplant-eligible patients with newly diagnosed multiple myeloma.
Click to read the study in The Lancet Oncology
In-Depth [randomized controlled trial]: This study was a long-term follow-up of the CASSIOPEIA trial, which evaluated the efficacy of adding daratumumab to bortezomib, thalidomide, and dexamethasone (D-VTd) in transplant-eligible patients with newly diagnosed multiple myeloma. This study recruited patients from 111 European centers and included 1085 patients aged 18-65 with an ECOG performance score of 0-2. In Part 1, patients were randomly assigned to either D-VTd or VTd as induction and consolidation therapy. In Part 2, those who completed consolidation with a partial response or better were re-randomized to receive either daratumumab maintenance therapy or observation.
The results showed that progression-free survival was significantly longer in the daratumumab maintenance group compared to the observation group, with a median progression-free survival not reached versus 45.8 months, respectively (HR 0.49, p<0.0001). Additionally, the D-VTd induction and consolidation group had a median progression-free survival of 83.7 months compared to 52.8 months in the VTd group (HR 0.61, p<0.0001). The study also reported improved minimal residual disease (MRD) negativity rates in the daratumumab groups. Specifically, 58.1% of patients in the D-VTd plus daratumumab group achieved MRD negativity as compared to 48.9% in the D-VTd plus observation group (OR 1.56, p=0.031). Overall survival from the first randomization was also longer in the D-VTd group (HR 0.55, p<0.0001). These findings overall support the addition of daratumumab to both induction and maintenance therapy to improve long-term outcomes in patients with newly diagnosed multiple myeloma.
Image: PD
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