PS1414 A PHASE 1B/2 STUDY OF SELINEXOR, CARFILZOMIB, AND DEXAMETHASONE (SKD) IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)
Notice bibliographique
Résumé
Background: The management of relapsed myeloma continues to evolve including the dose and schedule of carfilzomib (carfil) with increasing use of once weekly (QW) IV carfil as opposed to twice weekly (BIW) administration. Selinexor in combination with dexamethasone (dex) has demonstrated a 26.2% ORR in pts with triple‐class refractory myeloma (defined as refractory to an immunomodulatory imide drug [IMiD], proteasome inhibitor [PI] and anti‐CD‐38 monoclonal antibody [mAb]) including deep responses with 6 very good partial response (VGPR) and 2 pts in a stringent complete response (sCR) (minimal residual disease negative). Jakubowiak et al. have previously demonstrated that BIW selinexor can be safely combined with BIW carfil with an ORR of 63% ( ASH 2016 ). Given the increasing use of QW carfil, we have initiated a phase 1 study to determine the recommended phase 2 dose(RP2D) of QW selinexor in combination with carfil/dex. Aims: The primary objectives of the study were to determine the maximum tolerated dose (MTD), RP2D, and to assess the safety, tolerability, and preliminary efficacy of the combination of SKd in pts with RRMM. Methods: This is amulticenter, open‐label study. Pts whose MM is relapsing, is not refractory to carfil, and may have had prior PI exposure were eligible. Selinexor was dosed QW at 80 or 100 mg. Carfil was dosed QW at 56 mg/m 2 or 70 mg/m 2 . Dex was given at 40 mg QW. Results: As of February 20 th , 2019, 9 pts were enrolled in the study. Of these, 3 were male and 6 were female. The median age was 71 years (range 50 – 76) and the median number of prior treatments was of 4 (range 2 – 8) prior treatment regimens. All 9 pts were carfil naïve. Seven of 9 pts were refractory to prior treatment with bortezomib. Eight pts were refractory to prior lenalidomide (len) or pomalidomide (pom) treatment including 3 pts refractory to both len and pom. Five pts were refractory to prior dara treatment. Six dose limiting toxicities (DLTs) were observed, which can be seen in Table 1 . Common treatment‐related Grade 1/2 adverse events (AEs) included: nausea (6 pts), anemia (3 pts), fatigue (3 pts), and leukopenia (3 pts). Grade 3/4 AEs included: thrombocytopenia (5 pts), hyperglycemia (2 pts), and anemia (2 pts). Eight pts were evaluable for response and the ORR was 75% including (1 complete response, 4 VGPR, 1 unconfirmed VGPR); the patient with unconfirmed VGPR is still on study. Two pts had stable disease. One pt is pending response evaluation. As of February 20 th , 6 pts remain on treatment. Summary/Conclusion: The combination of SKd has demonstrated encouraging preliminary activity with an ORR of 75%. No unexpected AEs were noted. Phase 1 dose escalation of the combination of SKd will define the optimal RP2D. image
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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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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) | 0,001 | 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 ».