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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-01

AUTHORS

Jonathan L. Kaufman, Roberto Mina, Andrzej J. Jakubowiak, Todd L. Zimmerman, Jeffrey J. Wolf, Colleen Lewis, Charise Gleason, Cathy Sharp, Thomas Martin, Leonard T. Heffner, Ajay K. Nooka, R. Donald Harvey, Sagar Lonial

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/m2 (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). More... »

PAGES

3

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41408-018-0154-8

DOI

http://dx.doi.org/10.1038/s41408-018-0154-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111099501

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30610196


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