Phase II Study of Isatuximab, and Weekly Carfilzomib + Dexamethasone in Relapsed and Refractory Multiple Myeloma (RRMM)
Notice bibliographique
Résumé
Background: Isatuximab (Isa) is a humanized anti-CD38 monoclonal antibody that has been shown to have multiple direct antitumor and immunomodulatory activities.1 Isatuximab is approved for use in combination with pomalidomide and dexamethasone (ICARIA) and twice weekly carfilzomib (K) and dexamethasone (IKEMA) as salvage treatment for patients with RRMM. In the IKEMA study the PFS was 35.7 months in patients with early relapsed MM (1-3 prior LOT).2 Multiple three-drug combination studies have demonstrated the safety and efficacy of using once weekly, high-dose K at 70 mg/m2 Day 1, 8, 15.3,4 Objectives: The aim of this study was to assess the safety and efficacy of Isa-Kd utilizing standard Isa-dosing (10 mg/kg QWk x4, then QOWk) and weekly high-dose K (70 mg/m2) plus dexamethasone (d) in patients with early relapsed MM (1-3 prior LOT). (NCT-02332850) Methods: Eligible patients (pts) had disease progression after 1-3 prior LOT, an ECOG <3, no prior CD38 therapy, and adequate organ function. Therapy included Isa IV weekly (QW) for 4 doses then Q2W together with K (20mg/m2 Day 1, =>70 mg/m2: Day 8, 15 Q28d and for all subsequent K doses) and d (40 mg PO QW). Pts continued therapy until disease progression, undue toxicity or physician/patient choice. Results: As of July 14, 2024,50 pts have been enrolled and are evaluable for safety and response. Pts were ECOG <2, had a median age of 64 (range 39-78) yrs, received a median of 1 LOT (range 1-3) and 90% had received prior SCT. All pts were IMiD and PI exposed, 50% Len refractory (Refr), and 22% had received prior K. Median follow-up is 14 months (range 2-43m), and a median of 16 cycles of Isa-Kd have been administered. The ORR is 90% (sCR/CR 8, VGPR 21, PR 16), responses occur rapidly (median 1 cycle) and responses deepen over time. The median progression free and overall survival have not been reached. Disposition: 14 patients have progressed; 3 patients have died (1 from PD, 1 sudden death attributed to K, 1 sudden death off treatment), 17 pts stopped treatment in response (7 due to toxicity (3 SOB, 1 MI, 1 FTT, 1 colitis, 1 fatigue); 6 for treatment holiday; 4 due to physician choice, and 16 remain on therapy). The most frequent occurring treatment-related toxicity (AEs-all grades, incidence ≥ 20%), were infusion related reactions (IRR; 58%), hypertension (52%), nausea (50%), cough (42%), fatigue (40%), dyspepsia (40%), insomnia (38%), diarrhea (38%), thrombocytopenia (34%), fever (26%), headache (24%), constipation (22%), and anemia (20%). Infections were also common; 30 pts (60%) experienced an URI, 10 pts (20%) had covid, and an additional 17 pts experienced a presumed bacterial infection (5 sinusitis, 4 UTI, 3 pneumonia, 3 cellulitis, 2 colitis). The IRRs were all attributable to Isa, all were Grade 1-2 and only 2 pts had a subsequent or second IRR. Conclusion: The triplet combination of Isa-Kd incorporating weekly high-dose K70 mg/m2 appears safe; with no unexpected toxicity and AEs consistent with the toxicity profile of the individual agents. Encouraging anti-MM activity has been demonstrated with an ORR of 90% in patients with early RRMM (1-3 PLOT) and the median PFS and OS have not been reached (NCT 02332850).
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,002 | 0,000 |
| Intégrité de la recherche | 0,002 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».