Minimal residual disease (MRD) negativity (neg) in patients (pts) with relapsed or refractory multiple myeloma (RRMM) treated with belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide, bortezomib, and dexamethasone (PVd): Analysis from the DREAMM-8 trial.
Bibliographic record
Abstract
7515 Background: In DREAMM-8 (NCT04484623), BPd demonstrated a statistically significant, clinically meaningful benefit to progression-free survival (PFS) vs PVd in pts with RRMM who received ≥1 prior line of treatment including lenalidomide. MRD neg has been shown to be a predictor of PFS and overall survival (OS) in MM. We assessed efficacy outcomes by MRD status. Methods: Ptswere randomized (1:1) to BPd or PVd. The primary endpoint was independent review committee (IRC)–assessed PFS; OS, duration of response, and MRD status determined by next-generation sequencing with 10 −5 sensitivity threshold was assessed in pts with complete response or better (≥CR) every 6 mo until progressive disease. Post hoc subgroup analyses of PFS and OS were conducted based on IRC-assessed response (≥CR or ≥VGPR) and MRD-neg status using Kaplan-Meier method; CIs were estimated using Brookmeyer-Crowley method. Results: 302 pts were randomized to BPd (n=155) or PVd (n=147). As previously reported (median follow-up, 21.8 mo), more pts with BPd had CR-based MRD neg vs PVd (37/155 [24%] vs 7/147 [5%]). A similar trend was seen in pts with ≥VGPR; 50/155 pts (32%) had VGPR-based MRD neg with BPd vs 8/147 (5%) with PVd. In the DREAMM-8 trial, MRD neg was associated with improved efficacy outcomes (Table). Pts with CR-based MRD neg had a lower risk of disease progression or death compared with pts without MRD neg (PFS HR, 0.14; 95% CI, 0.06-0.32; Table); median was NR overall and in each treatment arm (HR [BPd vs PVd], 0.90; 95% CI, 0.10-7.76). MRD neg pts had a lower risk of death (OS HR, 0.18; 95% CI, 0.07-0.49). In all pts who did not have CR-based MRD neg, pooled median PFS was 14.0 mo (95% CI, 11.1-18.6 mo; BPd, 19.6 mo; PVd, 10.2 mo; HR [BPd vs PVd], 0.67; 95% CI, 0.47-0.94), and the pooled 18-mo PFS rate was 46% (95% CI, 39%-52%; BPd, 52%; PVd, 39%). Median OS was NR overall, 33.0 mo (95% CI, 23.7-NR) with BPd and NR with PVd; 18-mo OS rate was 69% (95% CI, 63%-75%; BPd, 72%; PVd, 67%). Conclusions: Consistent with previous reports, MRD neg was associated with a robust benefit in PFS and OS, highlighting the significance of a greater response depth. Pts with BPd achieved a 5-fold improvement in CR-based MRD neg vs PVd (24% vs 5%). Pts who did not achieve CR-based MRD neg had a clinically meaningful benefit in PFS with BPd vs PVd. Clinical trial information: NCT04484623 . MRD neg Non-MRD neg MRD status (≥CR), n Pooled (44) BPd (37) PVd (7) Pooled (258) BPd (118) PVd (140) Median PFS (95% CI), mo NR (NR-NR) NR (NR-NR) NR (NR-NR) 14.0 (11.1-18.6) 19.6 (13.5-NR) 10.2 (8.4-17.1) 18-mo PFS rate (95% CI), % 93 (79-98) 91 (75-97) 100 (100-100) 46 (39-52) 52 (42-62) 39 (30-48) 18-mo OS rate (95% CI), % 93 (80-98) 92 (76-97) 100 (100-100) 69 (63-75) 72 (62-79) 67 (59-74)
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".