B08 IDECABTAGENE VICLEUCEL VERSUS STANDARD REGIMENS IN PATIENTS WITH TRIPLE-CLASS–EXPOSED RELAPSED AND REFRACTORY MULTIPLE MYELOMA: KARMMA-3 A PHASE 3 RANDOMIZED CONTROLLED TRIAL
Bibliographic record
Abstract
Background: Survival outcomes are poor in patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class–exposed (TCE) to immunomodulatory (IMiD®) agents, proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies. As patients become TCE in earlier lines of therapy, treatment options are limited. Idecabtagene vicleucel (ide-cel) demonstrated deep durable responses in heavily pretreated TCE RRMM. Methods: KarMMa-3 (NCT03651128), an international, open-label, randomized controlled trial, enrolled patients with RRMM who received 2–4 prior regimens, including an IMiD agent, PI, and daratumumab, and refractory to the last regimen. Patients were randomized 2:1 to ide-cel or a standard regimen (investigator choice of daratumumab + pomalidomide + dexamethasone, daratumumab + bortezomib + dexamethasone, ixazomib + lenalidomide + dexamethasone, carfilzomib + dexamethasone, or elotuzumab + pomalidomide + dexamethasone based on prior regimen). Ide-cel was infused at a target dose of 150–450×106 chimeric antigen receptor-positive (CAR+) T cells (≤540×106 cells allowed). Primary endpoint: progression-free survival (PFS) assessed by Independent Response Committee (IRC). Key secondary endpoints: IRC-assessed overall response rate (ORR) and overall survival. Other secondary endpoints: duration of response (DOR), health-related quality of life (QoL), pharmacokinetics, and safety. Efficacy assessed per ITT. Results: Of 386 patients (ide-cel n=254, standard regimens n=132), 225 received ide-cel (median dose 445×106 CAR+ T cells [range 175–529×106]) and 126 received standard regimens. Baseline characteristics, including median age (63 years), median time since diagnosis (4.1 years), median prior therapies (n=3), triple-class (66%) and daratumumab (95%) refractoriness, and high-risk cytogenetics (44%), were generally balanced. Median follow-up from randomization to data cutoff was 18.6 months. Ide-cel significantly improved PFS versus standard regimens (median 13.3 vs 4.4 months, HR 0.49, P<0.0001). Ide-cel significantly improved ORR versus standard regimens (71% vs 42%, P<0.0001), with deeper (complete response 39% vs 5%), more durable responses (median DOR 14.8 vs 9.7 months). PFS and ORR benefit of ide-cel was consistent across multiple patient subgroups. Post–ide-cel infusion, CAR+ T cells underwent rapid multi-log expansion (median 11 days to maximum expansion). In the treated population, grade 3/4 adverse events (AEs) occurred in 93% and 75% of patients in the ide-cel and standard regimen arms, respectively, and grade 5 AEs in 14% and 6%; grade 5 treatment-related AEs in 3% and 1%. In ide-cel-treated patients any grade cytokine release syndrome occurred in 88%; grade 3/4 in 4%. Any grade investigator-identified neurotoxicity occurred in 15% of patients; grade 3/4 in 3%. Ide-cel demonstrated clinically meaningful improvements on patient-reported outcomes, including symptoms, functioning, and QoL versus standard regimens (Figure). Conclusions: Ide-cel treatment resulted in a significant improvement in PFS and ORR, with deeper and more durable responses versus standard regimens. Ide-cel benefit was consistent across difficult-to-treat subgroups. The toxicity profile of ide-cel was consistent with prior studies. These results support the use of ide-cel in patients with early relapse TCE RRMM, a population with poor survival outcomes. This abstract is an encore previously submitted at ASTCT 2023.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| 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".