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)

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

Mina R.
Co-first
;
2019-01-01

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)
2019
9
1 (Article number 3)
1
9
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/
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
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.
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Descrizione: [Published Vsn.] Kaufman JL, Mina R et al. Blood Cancer J . 2019 Jan 4;9(1):3. doi: 10.1038/s41408-018-0154-8. © The Author(s) 2019. Open access article. a Creative Commons Attribution 4.0 International License. Available at: https://www.nature.com/articles/s41408-018-0154-8 | https://doi.org/10.1038/s41408-018-0154-8
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1732448
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