Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results
Bibliographic record
Abstract
ABSTRACT: Previous results from CASSIOPEIA demonstrated superior progression-free survival (PFS) and minimal residual disease (MRD) negativity with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (VTd) induction/consolidation and with daratumumab maintenance vs observation in transplant-eligible, newly diagnosed multiple myeloma. Here, we present long-term MRD status and PFS outcomes after a median follow-up of 80.1 months. Patients were randomly assigned (1:1) to daratumumab plus VTd (D-VTd) or VTd induction/consolidation; patients remaining on study were rerandomized to daratumumab maintenance or observation for ≤2 years. MRD status was assessed at predefined time points during each study phase. D-VTd improved overall MRD-negativity rates (10-5) after induction (34.6% vs 23.1%) and consolidation (63.7% vs 43.7%) and provided PFS benefit, regardless of postinduction MRD status, vs VTd alone. Daratumumab maintenance improved overall MRD-negativity rates over observation, regardless of induction/consolidation treatment (D-VTd/daratumumab vs D-VTd/observation, 10-5 [77.3% vs 70.7%] and 10-6 [60.7% vs 52.0%]; VTd/daratumumab vs VTd/observation, 10-5 [70.9% vs 51.2%] and 10-6 [48.4% vs 30.7%]) and improved MRD-negativity rates, regardless of risk status, as defined by cytogenetic abnormalities or the revised International Staging System score. Furthermore, daratumumab maintenance provided PFS benefit vs observation, regardless of induction/consolidation treatment and postconsolidation MRD status. D-VTd followed by daratumumab maintenance consistently produced the highest landmark, cumulative, and sustained MRD-negativity rates (10-5 and 10-6), translating to superior long-term PFS outcomes. These results demonstrate that daratumumab-based induction/consolidation followed by daratumumab maintenance resulted in the deepest and most durable MRD negativity, leading to superior PFS outcomes. This trial was registered at www.clinicaltrials.gov as #NCT02541383.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".