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CASSIOPEIA: Long-term MRD results of D-VTd in NDMM
The Multiple Myeloma Hub has previously reported the CASSIOPEIA part 1 and part 2 study design. In the maintenance phase, patients were rerandomized to receive either D-VTd/DARA (n = 229), D-VTd/OBS (n = 229), VTd/DARA (n = 213), or VTd/OBS (n = 215) for 2 years. The maintenance phase endpoint included MRD status and PFS after a median follow-up of 80.1 months.
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Key learnings1 |
MRD negativity (10–5) rates were higher with D-VTd vs VTd post-induction (34.6% vs 23.1%, OR 1.76; p < 0.0001) and post-consolidation (63.7% vs 43.7%, OR 2.26; p < 0.0001). |
MRD negativity rates were highest among patients who received D-VTd/DARA vs D-VTd/OBS (10–5; 77.3% vs 70.7%, OR 1.76; p = 0.0417; and 10–6; 60.7% vs 52.0%, OR 1.55; p = 0.0365). |
MRD negativity rates were also high among patients who received VTd/DARA vs VTd/OBS (10–5; 70.9% vs 51.2%, OR 3.16; p < 0.0001; and 10–6; 48.4% vs 30.7%, OR 2.41; p < 0.0001). |
MRD-negative rates improved in patients who received D-VTd/DARA or VTd/DARA vs OBS, irrespective of age, ISS stage, or cytogenetic risk. |
Patients who received D-VTd/DARA vs OBS showed higher rates of sustained MRD negativity at ≥12 months (10–5, 65.5%; 10–6, 49.3%), ≥24 months (10–5, 58.5%; 10–6, 41.9%), and ≥36 months (10–5, 43.7%; 10–6, 29.7%). |
DARA maintenance improved PFS vs OBS in both MRD-negative (HR, 0.54; p = 0.0007) and MRD-positive patients (HR, 0.48; p < 0.0001). |
This long-term comprehensive analysis shows that the addition of DARA to induction/consolidation and maintenance resulted in deep and durable MRD negativity. DARA also provided PFS benefit vs OBS regardless of MRD status or prior induction/consolidation therapy. |
Abbreviations: DARA, daratumumab; D-VTd, daratumumab, bortezomib, thalidomide, dexamethasone; HR, hazard ratio; ISS, International Staging System; MRD, measurable residual disease; NDMM, newly diagnosed multiple myeloma; OBS, observation; OR, odds ratio; PFS, progression-free survival; VTd, bortezomib, thalidomide, dexamethasone.
References
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