S195: IDECABTAGENE VICLEUCEL (IDE-CEL) VS STANDARD REGIMENS IN PATIENTS WITH TRIPLE-CLASS–EXPOSED (TCE) RELAPSED AND REFRACTORY MULTIPLE MYELOMA (RRMM): A KARMMA-3 ANALYSIS IN HIGH-RISK SUBGROUPS
Notice bibliographique
Résumé
Background: Despite improvements in the treatment landscape of RRMM with the use of combination therapy, with immunomodulatory (IMiD®) agents, proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies in front-line and early relapse, patients are becoming TCE earlier in their treatment course. Outcomes in patients with high-risk disease characteristics such as cytogenetic abnormalities, advanced-disease stage, high tumor burden, presence of extramedullary plasmacytoma (EMP), and triple-class–refractory (TCR) disease also remain poor. Ide-cel, a BCMA-directed CAR T cell therapy, significantly improved median progression-free survival (mPFS; 13.3 vs 4.4 months [mo]; HR, 0.49; P<0.0001) and overall response rates (ORR; 71 vs 42%, P<0.001) vs standard (std) regimens in the overall population of patients with TCE RRMM in KarMMa-3 (NCT03651128; Rodríguez-Otero NEJM 2023; DOI: 10.1056/NEJMoa2213614). Aims: To assess the efficacy and safety of ide-cel vs std regimens in patients with high-risk disease characteristics in KarMMa-3. Methods: In KarMMa-3, patients with RRMM who received 2–4 prior regimens, who were TCE (IMiD agent, PI, and daratumumab), and had disease refractory to the last regimen, were randomized 2:1 to receive ide-cel (target dose range: 150–450 x 106 CAR+ T cells) or a std regimen (DPd, DVd, IRd, Kd, or EPd, based on prior regimen, per investigator). Efficacy (PFS, ORR, and complete response rate [CRR]) was assessed in high-risk groups including patients with cytogenetic abnormalities (del[17p], t[4;14], or t[14;16]), R-ISS stage III disease, high tumor burden (≥50% CD138-positive plasma cells in bone marrow), EMP (soft-tissue–only and soft-tissue bone-related plasmacytomas), and TCR (refractory to ≥1 each of an IMiD agent, a PI, and an anti-CD38 antibody). Results: Baseline demographics and high-risk disease characteristics were balanced between treatment arms. Median time to progression on the last prior regimen was short in patients treated with both ide-cel vs std regimens in all high-risk subgroups: cytogenetic abnormalities (5.6 vs 6.7 mo), R-ISS stage III disease (3.9 vs 3.5 mo), high tumor burden (5.1 vs 6.2 mo), EMP (5.1 vs 5.1 mo), and TCR disease (5.6 vs 5.8 mo). At a median follow-up of 18.6 mo (range, 0.4–35.4), mPFS was longer in patients treated with ide-cel vs std regimens in all high-risk subgroups: cytogenetic abnormalities (11.9 vs 4.2 mo; HR, 0.608), R-ISS stage III disease (5.2 vs 3.0 mo; HR, 0.861), high tumor burden (11.0 vs 4.9 mo; HR, 0.595), EMP (7.2 vs 2.0 mo; HR, 0.401), and TCR disease (11.2 vs 3.5 mo; HR, 0.458; Table). ORRs were improved with ide-cel vs std regimens, regardless of the presence of high-risk disease characteristics. Similarly, CRRs were improved in patients treated with ide-cel vs std regimens in all high-risk subgroups: cytogenetic abnormalities (31.8 vs 4.9%), R-ISS stage III (16.1 vs 7.1%), high tumor burden (31.0 vs 8.8%), EMP (23.0 vs 3.1%), and TCR disease (33.5 vs 1.1%). Safety data will be presented. Summary/Conclusion: Patients treated with ide-cel had a lower risk of disease progression or death and higher odds of achieving an overall response (with higher CRRs) compared with patients who received std regimens, regardless of baseline high-risk disease. Overall, these results support use of ide-cel in patients with TCE RRMM, including patients with difficult-to-treat, high-risk disease.Keywords: Clinical trial, Multiple myeloma, High risk, CAR-T
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,005 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».