Quadruplet regimens for patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis
Bibliographic record
Abstract
ABSTRACT: Quadruplet regimens (anti-CD38 monoclonal antibodies [mAbs] with proteasome inhibitor [PI] and immunomodulatory drugs [IMiDs]) are increasingly being investigated in newly diagnosed multiple myeloma (NDMM). The objective of our study was to conduct a systematic review and meta-analysis to measure the efficacy and toxicity of quadruplet regimens used in NDMM. Embase, MEDLINE, Web of Science, Cochrane Library, clinical trial registries, and meeting libraries from inception to 24 January 2024, in addition to American Society of Clinical Oncology conference abstracts 2024, were searched using terms reflecting multiple myeloma and components of the quadruplet regimen. Included studies were randomized controlled trials (RCTs) that compared backbone regimens consisting of a PI and IMiD vs the same regimen plus an anti-CD38 mAb in NDMM. We identified 7 RCTs including 3716 patients. Compared with triplets, quadruplets increase the overall response rate (ORR; relative risk [RR], 1.03; 95% confidence interval [CI], 1.01-1.05) and progression-free survival (PFS; hazard ratio [HR], 0.55; 95% CI, 0.46-0.66). Quadruplets increase the rates of minimal residual disease (MRD) negativity at 10-5 (RR, 1.39; 95% CI, 1.23-1.58) and 10-6 (RR, 1.62; 95% CI, 1.36-1.94). Quadruplets improve overall survival (OS; HR, 0.65; 95% CI, 0.53-0.79). There was a slight increase in the rates of grade 3 to 4 infections (RR, 1.22; 95% CI, 1.07-1.39) noted with quadruplets compared with triplets. Overall, in this meta-analysis, quadruplets were associated with improved efficacy including ORR, MRD negativity, PFS, and OS, with a slight increase in infection rates. Quadruplet regimens represent a new standard of care, particularly in transplant-eligible NDMM.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.011 | 0.003 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".