DARATUMUMAB + BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE (DVRD) VS VRD IN TRANSPLANT-INELIGIBLE (TIE)/TRANSPLANT-DEFERRED (TD) NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): PHASE 3 CEPHEUS TRIAL CYTOGENETIC SUBGROUP ANALYSIS
Why this work is in the frame
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Bibliographic record
Abstract
In CEPHEUS, DVRd significantly improved overall MRD negativity (MRD neg + ≥CR) and sustained MRD neg rates and PFS in patients (pts) with TIE/TD NDMM. In this post hoc analysis, we report outcomes in cytogenetic risk subgroups. To gain additional insight into those patients who had long-term clinical benefit ≥5 years after a single cilta-cel infusion, we conducted a post hoc analysis. We report OS, ≥5-year progression-free outcomes, associated biomarkers, and safety from CARTITUDE-1, with 61.3-month median follow-up. Pts with TIE/TD NDMM were randomized 1:1 to DVRd or VRd. High-risk (HiR) cytogenetic abnormalities (HRCAs) were assessed by FISH. HiR was ≥1 of: del(17p); t(4;14); t(14;16). Revised HiR (R-HiR) was ≥1 of above or gain (3 copies) or amp(1q) (≥4 copies). Standard risk (SR) was 0 HRCAs; revised SR (R-SR) was 0 revised HRCAs. Additional risk groups included: gain or amp(1q) + other HRCAs; 1 and ≥2 revised HRCAs. We assessed overall MRD neg rate, sustained MRD neg, ≥CR rate, and PFS. We reported all MRD neg rates at 10-5 unless noted. Of 395 randomized pts (DVRd, n = 197; VRd, n = 198), 298 had SR (DVRd, n = 149; VRd, n = 149) and 52 HiR (DVRd, n = 25; VRd, n = 27). 184 pts had R-SR (DVRd, n = 94; VRd, n = 90) and 167 R-HiR (DVRd, n = 83; VRd, n = 84). At median 58.7-month (mo) follow-up, overall MRD neg rate was higher with DVRd vs VRd in SR (64% vs 38%; P < 0.0001) and R-SR pts (68% vs 38%; P < 0.0001). Rates by treatment (tx) arm in HiR (48% vs 56%; P = 0.7816) and R-HiR pts (55% vs 45%; P = 0.2169) were comparable. DVRd improved ≥1-year (y) sustained MRD neg rate vs VRd in SR (51% vs 26%; P < 0.0001) and R-SR pts (54% vs 24%; P < 0.0001). Sustained MRD neg rates by tx arm were comparable in HiR (40% vs 37%; P = 1.0000) and R-HiR pts (43% vs 30%; P = 0.0782). PFS was improved with DVRd vs VRd in SR (HR = 0.61 [95% CI, 0.41–0.91]; P = 0.01) and R-SR (HR = 0.54 [95% CI, 0.32–0.91]; P = 0.01) pts and was comparable by tx arm in HiR (HR = 0.88 [95% CI, 0.48–1.84]; P = 0.73); and R-HiR HR = 0.73[95% CI, 0.46–1.15]; P = 0.17; pts (), including in MRD neg pts (R-SR: (HR = 0.63 [95% CI, 0.26–1.52]; P = 0.30); R-HiR: HR = 0.71 [95% CI, 0.32–1.58]; P = 0.39. Gain(1q)+otherHRCAs HR = 0.80[95% CI, 0.45–1.42]; P = 0.044; Amp(1q)+other HRCAs HR = 0.97 [95% CI, 0.38–2.47]; P = 0.95. 1 revised HRCA HR = 0.63[95% CI, 0.37–1.09]; P = 0.09; ≥2 revised HRCA (HR = 1.01[95% CI, 0.42–2.44]; P = 0.98) Remaining outcomes, including rates of ≥CR, ≥2-y sustained MRD neg, and overall and ≥1-y sustained MRD neg at 10-6, were improved with DVRd in SR and R-SR pts and comparable by tx arm in HiR and R-HiR pts. In CEPHEUS, DVRd consistently improved the key response outcomes of MRD neg and PFS in (R-)SR pts. In HiR pts, MRD and PFS outcomes trended lower in both tx arms vs those in SR pts. Here, DVRd mostly improved PFS outcomes vs VRd; however, pt numbers were small, with the study underpowered for HiR pts. These data support use of DVRd for TIE/TD NDMM regardless of cytogenetic risk status. This study was funded by Johnson & Johnson. Medical writing support was provided by Maggie Hartman, PharmD, of Eloquent Scientific Solutions, and funded by Johnson & Johnson.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 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 it