High-Dose Cyclophosphamide in Highly Refractory Multiple Myeloma Patients As a Bridge to Further Novel Therapies
Notice bibliographique
Résumé
Abstract Background: Despite major advances in the treatment of multiple myeloma with novel therapies including proteozome inhibitors and immunomodulatory drugs, most patients during the course of their disease will become refractory to all agents. The prognosis of such patients is very poor. Some patients have extensive bone marrow involvement with resulting cytopenias, making them ineligible for clinical trials. The alternative route using aggressive cytoreduction therapies such as VTD-PACE, DCEP, V-DCEP, may have a limited role to serve as debulking agents and as a bridge to a next line of therapy because of their overwheming toxicity. In this pilot study, we chose to treat refractory patients with single agent high dose cyclophosphamide (HDCY), combined with dexamethasone, with the aim to bridge responding patients to a next line of therapy. Objectives: Primary outcome: to assess overall response rate (ORR). Secondary outcomes: to assess progression free survival (PFS) and overall survival (OS). Methods: Prospective cohort study of patients treated between April 2013 and April 2016 at the Montreal Jewish General Hospital with HDCY, 1.2gr/m2, day 1 and 3, q21days x 4, and dexamethasone, 40mg PO, Q week. All patients received neupogen and levaquin as prophylaxis. PFS was defined as the time between initiation of HDCY and the date of first documented disease progression or death from any cause. Response was assessed by IMWG 2014 criteria. Responders included patients achieving ≥ PR. Kaplan Meier method was used to calculate progression-free and overall survival. Results: A total of 18 patients was included in the analysis. The median age was 61years (range, 44-71), median time from diagnosis until HDCY treatment was 57 months (range, 5-108). Patients were heavily pretreated, with median 4 prior lines of therapy (range, 1-7). All patients had been refractory to their last line of therapy. Seventeen patients (94%) were refractory to both bortezomib and lenalidomide containing regimens, and sixteen patients (88%) had an ASCT. Median number of HDCY cycles administered was 4 (range, 2-5). Median follow up was 10 months. ORR to HDCY was 55%, with three patients achieving CR (15%). Twelve patients (67%) went on to further therapies after achieving at least stable disease. Median PFS was 6 months, and median OS was 12 months. This regimen was complicated almost exclusively by hematological toxicity, with 14 out 18 patients experiencing G4 neutropenia. Thirteen patients were admitted for febrile neutropenia. There were no treatment related mortality. Conclusion: HDCY with dexamethasone has proven to be in this small prospective study a highly efficient rescue regimen for double refractory, advanced stage disease myeloma patients, providing the opportunity to bridge the majority of these patients to further novel therapies, also including a second ASCT. Disclosures Shamy: Celgene: Honoraria, Other: Advisory board; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 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 ».