Phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in patients with relapsed and/or refractory multiple myeloma
Corresponding Author
David H. Vesole
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Correspondence: David H. Vesole, Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, 92 2nd Street #340, Hackensack, NJ 07601, USA.
E-mail: [email protected]
Search for more papers by this authorElizabeth Bilotti
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorJoshua R. Richter
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorAnn McNeill
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorLaura McBride
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorLaura Raucci
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorPalka Anand
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorUrszula Bednarz
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorKristin Ivanovski
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorJudith Smith
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorVeena Batra
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorAdolfo Aleman
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorTaliah Sims
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorLaura Guerrero
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorAnthony Mato
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorDavid S. Siegel
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorCorresponding Author
David H. Vesole
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Correspondence: David H. Vesole, Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, 92 2nd Street #340, Hackensack, NJ 07601, USA.
E-mail: [email protected]
Search for more papers by this authorElizabeth Bilotti
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorJoshua R. Richter
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorAnn McNeill
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorLaura McBride
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorLaura Raucci
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorPalka Anand
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorUrszula Bednarz
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorKristin Ivanovski
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorJudith Smith
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorVeena Batra
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorAdolfo Aleman
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorTaliah Sims
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorLaura Guerrero
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorAnthony Mato
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorDavid S. Siegel
Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA
Search for more papers by this authorSummary
Research has shown that proteasome inhibitors (e.g., carfilzomib), immunomodulatory agents (e.g., lenalidomide), histone deacetylase inhibitors (e.g., vorinostat) and corticosteroids (e.g., dexamethasone) have synergistic anti-multiple myeloma (MM) activity. This phase I dose-escalation study evaluated a regimen combining carfilzomib, lenalidomide, vorinostat and dexamethasone (QUAD) in patients with relapsed and/or refractory MM. Seventeen patients received carfilzomib (15, 20, or 20/27 mg/m2; 30-min infusion; days 1, 2, 8, 9, 15, 16), lenalidomide (15 or 25 mg; days 1–21), vorinostat (300 or 400 mg; days 1–7, 15–21), and dexamethasone (40 mg; days 1, 8, 15, 22) in 28-d cycles. No dose-limiting toxicities were observed; the maximum tolerated dose was not reached. The maximum administered dose was carfilzomib 20/27 mg/m2, lenalidomide 25 mg, vorinostat 400 mg, and dexamethasone 40 mg. Common grade ≥3 adverse events included neutropenia (53%), thrombocytopenia (53%) and anaemia (41%). The overall response rate was 53%: 12% of patients achieved a very good partial response (PR) and 41% of patients achieved a PR. At a median follow-up of 10 months, median progression-free survival was 12 months and median overall survival was not reached. Treatment with QUAD was feasible and had encouraging activity in patients with relapsed and/or refractory MM.
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