Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplantineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial
Bibliographic record
Abstract
Patients with multiple myeloma (MM) meeting frailty criteria have worse outcomes than those identified as non-frail. Here, we present a post hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (N=265) versus VRd followed by Rd (N=181) in newly diagnosed transplant-ineligible MM (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score. Although patients aged >80 years were excluded, there was no exclusion for patients meeting frailty criteria. All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg once weekly; cycles 2-17, once every 2 weeks; subsequent cycles, once every 4 weeks). Patients with a frailty score of 0/1 were considered nonfrail; scores ≥2 were frail. Using this scoring, 26.7% of patients were frail (26.0% Isa-VRd; 27.6% VRd), and 72.0% non-frail (72.8% Isa-VRd; 70.7% VRd). After a median follow-up of 59.7 months, Isa-VRd significantly improved progression-free survival versus VRd in frail patients (hazard ratio [HR] =0.518; 95% confidence interval [CI]: 0.294-0.912; P=0.0227) and non-frail patients (HR=0.615; 95% CI: 0.419-0.903; P=0.0131). Significantly more frail patients receiving Isa-VRd than VRd achieved minimal residual disease negativity and complete response (odds ratio=3.459; 95% CI: 1.495-8.006; P=0.0030 at 10-5 by next-generation sequencing). Rates of treatment-emergent adverse events leading to definitive discontinuation were similar between both arms regardless of frailty status. This post hoc subgroup analysis of the IMROZ trial demonstrated that Isa-VRd is an effective option with a manageable safety profile for frail patients with Ti NDMM (clinicaltrials gov. Identifier: NCT03319667).
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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".