Distinct patient, tumour and chimeric antigen receptor T‐cell characteristics are associated with initiating versus sustaining responses to idecabtagene vicleucel in relapsed and refractory multiple myeloma
Bibliographic record
Abstract
Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)-directed autologous chimeric antigen receptor (CAR) T-cell therapy, was studied in relapsed and refractory multiple myeloma after >4 prior lines of therapy in KarMMa (NCT03361748). Translational analyses evaluated patient baseline, tumour and CAR T-cell features associated with initiating and sustaining response to a single ide-cel infusion. Baseline tumour burden, measured by soluble BCMA, and homeostatic cytokine levels released after lymphodepleting chemotherapy were among the top correlates for pharmacodynamic response. Duration of response was associated with tumour genomic features and quality of engraftment indicated by more robust CD4+ CAR T-cell expansion, higher levels of persistent ide-cel and sustained suppression of BCMA-expressing cells. A working model is proposed whereby patient and microenvironment features that may modulate ide-cel activation and expansion influence the probability of response initiation, and that tumour-intrinsic resistance features and sustained engraftment of ide-cel influence the durability of responses.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.001 | 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".