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ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)

David Siegel, MD
John Theurer Cancer Center
Hackensack, New Jersey, USA

06.13.14

Abstract No: 8535^

Background: Carfilzomib in combination with an immunomodulatory agent has proven efficacy in NDMM and RRMM. There is also synergistic activity of the combination of a proteasome inhibitor and a histone-deacetylase inhibitor

Methods: To determine the toxicity and activity of the quadruplet using carfilzomib with lenalidomide, vorinostat and dexamethasone. The primary objectives were to determine the maximum tolerated dose (MTD) and the safety/tolerability of QUAD. Secondary objectives included ORR, DOR, TTP and TTNT. All patients had relapsed or RRMM after at least one line of Tx. Tx consisted of 28-d cycles of lenalidomide d 1-21, vorinostat d 1-7 and 15-21, IV carfilzomib d 1, 2, 8, 9, 15 and 16 and IV/po dexamethasone 40 mg q wk. A standard 3+3 dose escalation schema to determine DLTs occurring in Cycle 1. AEs were graded using the NCI-CTCAE v3. Response was assessed by the modified IMWG criteria.

Results: As of January 20, 2014, 21 pts have been enrolled: 1 patient was replaced due to inability to complete Cycle 1 due to AE. Pt characteristics included: median age 61 yrs (range 48-71), 57% male, median # of prior regimens: 3 (range 1-9), median time from Dx: 4 years. All pts had prior autotransplant, 20 bortezomib, 20 lenalidomide and 4 vorinostat. AEs were experienced by 100% of pts including: anemia (16), fatigue (11), thrombocytopenia (14), neutropenia (12), muscle cramping (10) and diarrhea (9). 15 pts experienced ≥ grade 3 AEs: neutropenia (9), anemia (7), thrombocytopenia (9), infection (2), electrolyte imbalances (2), hyperglycemia (3), fatigue (1) constipation (1) and 1 death from progressive disease (PD). No DLTs were observed. The ORR was 53% and the CBR was 82%. 2 patients had PD as best response. 9 pts discontinued due to PD, 1 pt choice and 1 pt due to toxicity. 3 pts have completed 18 cycles.

Conclusions: QUAD is well tolerated in both relapsed and RRMM pts with no DLTs identified. The safety profile is manageable. The ORR of 53% and CBR of 82% are encouraging; the PFS is 12 months and OS not reached.

Clinical trial information: NCT01297764

Author(s): David H. Vesole, David Samuel DiCapua Siegel, Joshua Ryan Richter, Ann McNeill, Palka Anand, Urszula Bednarz, Kristin Ivanovski, Laura McBride, Laura Raucci, Veena Batra, Adolfo Aleman, Taliah Sims, Laura Guerrero, Judith Smith, Anthony R. Mato, Elizabeth Bilotti; John Theurer Cancer Center, Hackensack, NJ; Hackensack University Medical Center, Hackensack, NJ; Pharmacyclics, Inc., Sunnyvale, CA


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ASCO 2014: Overview of the ASCO 2014 Annual Meeting
ASCO 2014: Remission of Disseminated Cancer After Systemic Oncolytic Virotherapy (n.b., using modified measles vaccine)
ASCO 2014: Continuous treatment (CT) versus fixed duration of therapy (FDT) in newly diagnosed myeloma patients: PFS1, PFS2, OS endpoints.
ASCO 2014: DETERMINATION trial: A phase III multi-center study examining the timing of stem cell transplant for multiple myeloma
ASCO 2014: Continuous lenalidomide (LEN) therapy versus observation following nonimmunomodulatory compound-based induction therapy in newly diagnosed multiple myeloma (NDMM): MM-027 trial
ASCO 2014: MM-005: Phase 1 trial of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) in lenalidomide (LEN)-refractory and proteasome inhibitor (PI)-exposed myeloma
ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)
ASCO 2014: E1A06: A phase III trial comparing melphalan, prednisone, and thalidomide (MPT) versus melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed multiple myeloma (MM)
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ASCO 2014: A phase 1 (Ph1) trial of MK-3475 combined with lenalidomide (Len) and low-dose dexamethasone (Dex) in patients (pts) with relapsed/refractory multiple myeloma (RRMM)
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ASCO 2014: Treatment of relapsed/refractory multiple myeloma with weekly cyclophosphamide plus bortezomib plus prednisone or dexamethasone (CyBor-P/D): Updated experience at Princess Margaret Cancer Centre (PMCC)
ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)
ASCO 2014: SWOG 1211: A randomized phase I/II study of optimal induction therapy for newly diagnosed high-risk multiple myeloma (HRMM)
ASCO 2014: Results of the dose-escalation portion of a phase 1/2 study (CHAMPION-1) investigating weekly carfilzomib in combination with dexamethasone for patients with relapsed or refractory multiple myeloma
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ASCO 2014: A phase Ib dose escalation trial of SAR650984 (Anti-CD-38 mAb) in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma
ASCO 2014: Panorama 1: A randomized, double-blind, phase 3 study of panobinostat or placebo plus bortezomib and dexamethasone in relapsed or relapsed and refractory multiple myeloma
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ASCO 2014: Free light chain assay and cytogenetic abnormalities for identification of high-risk smoldering myeloma
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Myeloma Minute
March 5, 2015


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ASCO 2014: A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM)

David Siegel, MD
John Theurer Cancer Center
Hackensack, New Jersey, USA


Myeloma Minute
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