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
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».