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Author Notes:

Correspondence: Jonathan L. Kaufman Phone: +404 778 1900, Email: jlkaufm@emory.edu

Full list of author information is available at the end of the article.

Authors' contributions: J.L.K. and S.L. designed the study and supervised its conduct and the data analysis; J.L.K., A.J.J., T.L.Z., T.W., T.L.H., T.M., R.D.H., A.K.N., and S.L., recruited patients in the source studies and provided relevant data; R.M. collected, assembled, and analyzed the data; R.M. performed the statistical analysis; J.L.K. and R.M. drafted the initial manuscript; and all authors were given unrestricted access to the data, critically reviewed the manuscript drafts, approved the final version, and made the decision to submit the manuscript for publication.

These authors equally contributed: Jonathan L. Kaufman, Roberto Mina.

Conflict of interest: J.L.K. has consulted for Roche, AbbVie, Janssen, BMS, Takeda, and Karyopharm; A.J.J.: Consultant and Advisory Boards with honoraria for AbbVie, Amgen, BMS, Celgene, Karyopharm, SkylineDx, Takeda; L.T.H.: Pharmacyclics Institutional research funding and honorarium, Genentech institutional research funding; T.M. has received research support from Amgen and Sanofi-Aventis; J.W. has consulted for Takeda, Celgene, Amgen, and Novartis; R.D.H. research funding from Amgen and Novartis; A.K.N.: Advisory board: GSK, Spectrum, Celgene, Amgen, Novartis pharmaceuticals, Adaptive biotechnologies; Honorarium: BMS, Janssen pharmaceuticals; S.L. has consulted for Takeda, Celgene, Novartis, Janssen, GSK, BMS, and Merck. T.L.Z.: currently an employee of AbbVie.

Subject:

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

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Journal Title:

Blood Cancer Journal

Volume:

Volume 9, Number 1

Publisher:

, Pages 3-3

Type of Work:

Article | Final Publisher PDF

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)

Copyright information:

© 2019, The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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