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  1. Pubblicazioni

Combining carfilzomib and panobinostat to treat relapsed/refractory multiple myeloma: results of a Multiple Myeloma Research Consortium Phase I Study

Articolo
Data di Pubblicazione:
2019
Abstract:
Proteasome (PIs) and hystone deacetylase inhibitors (HDACis) have previously shown synergistic activity in the treatment of relapesed/refractory multiple myeloma (RRMM) patients. In this phase 1 study, we combined carfilzomib, a second generation PI, with panobinostat, a HDACi, to determine the maximum tolerated dose (MTD) of the combination (CarPan) and assess safety and efficacy among RRMM patients. Thirty-two patients (median of 4 prior lines of therapy) were enrolled. The MTD was carfilzomib 36 mg/m 2 (on days 1, 2, 8, 9, 15, and 16) and panobinostat 20 mg (TIW, 3 weeks on/1 week off, every 28 days), administered until progression. At the MTD, the most common grade 3/4, treatment-related adverse events were thrombocytopenia (41%), fatigue (17%), and nausea/vomiting (12%). The objective response rate (ORR) and clinical benefit rate were 63% and 68%, respectively. Median progression-free survival (PFS) and overall survival (OS) for the entire population were 8 and 23 months, respectively. No differences in terms of ORR (55% vs. 57%), median PFS (months 8 vs. 7 months) and OS (24 vs. 22 months) were observed between bortezomib-sensitive and -refractory patients. CarPan proved to be a safe and effective steroid-sparing regimen in a heavily pre-treated population of MM patients. (Trial registered at ClinicalTrial.gov: NCT01549431)
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multiple Myeloma; Odds Ratio; Oligopeptides; Panobinostat; Recurrence; Retreatment; Treatment Outcome
Elenco autori:
Kaufman J.L.; Mina R.; Jakubowiak A.J.; Zimmerman T.L.; Wolf J.J.; Lewis C.; Gleason C.; Sharp C.; Martin T.; Heffner L.T.; Nooka A.K.; Harvey R.D.; Lonial S.
Autori di Ateneo:
MINA Roberto
Link alla scheda completa:
https://iris.unito.it/handle/2318/1732448
Link al Full Text:
https://iris.unito.it/retrieve/handle/2318/1732448/592091/MINA_Blood_Jour_Cancer.pdf
Pubblicato in:
BLOOD CANCER JOURNAL
Journal
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Dati Generali

URL

https://www.nature.com/articles/s41408-018-0154-8; https://doi.org/10.1038/s41408-018-0154-8; https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30610196/
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