Comparative Efficacy of Talquetamab vs. Real-World Physician’s Choice of Treatment in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma: Updated Analyses of MonumenTAL-1 vs. LocoMMotion/MoMMent
Bibliographic record
Abstract
INTRODUCTION: Talquetamab, a bispecific antibody targeting GPRC5D, is approved for triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) based on results from MonumenTAL-1. We report updated indirect comparisons of talquetamab vs. real-world physician's choice of treatment (RWPC) in patients with TCE RRMM. METHODS: External control arms were created for three MonumenTAL-1 cohorts, two without prior T cell redirection (TCR) therapies who received subcutaneously administered talquetamab 0.4 mg/kg weekly (QW; n = 143) or 0.8 mg/kg every other week (Q2W; n = 154) and one with prior B cell maturation antigen (BCMA) TCR (n = 75) who received either schedule (median follow-up [mFU] 38.2, 31.2, and 30.3 months, respectively), from two real-world studies, LocoMMotion (mFU 26.4 months) and MoMMent (mFU 27.1 months). Imbalances in baseline covariates were adjusted using inverse probability weighting and multivariable regression. The relative effectiveness of talquetamab vs. RWPC was estimated for overall response rate (ORR), ≥ very good partial response (VGPR) rate, and ≥ complete response (CR) rate; odds ratios and relative response ratios (RRs) were derived from weighted logistic regression. Hazard ratios (HRs) for duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were estimated using a weighted Cox proportional-hazards model. RESULTS: In the TCR-naïve cohort, talquetamab Q2W had significantly improved outcomes vs. RWPC; RRs were ORR, 2.58; ≥ VGPR, 5.01; ≥ CR, 52.22 and HRs were DOR, 0.52 (p = 0.0011); PFS, 0.47; TTNT, 0.46; OS, 0.35 (all p < 0.0001). Results were similar in the QW cohort. The prior TCR cohort had favorable outcomes with talquetamab vs. RWPC; RRs were ORR, 3.03; ≥ VGPR, 4.88 and HRs were DOR, 0.09, (p = 0.0004); PFS, 0.30 (p < 0.0001); TTNT, 0.26 (p < 0.0001) and OS, 0.37 (p = 0.0020). CONCLUSION: With longer follow-up, these comparative analyses further demonstrate the clinical benefit of talquetamab over RWPC in patients with TCE RRMM, irrespective of prior TCR therapy. TRIAL REGISTRATION: MonumenTAL‑1, ClinicalTrials.gov identifier NCT03399799/NCT04634552; LocoMMotion, ClinicalTrials.gov identifier NCT04035226; MoMMent, ClinicalTrials.gov identifier NCT05160584.
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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 | 0.008 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".