title: Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma.
abstract: Treatment options for patients with heavily pretreated relapsed and/or refractory multiple myeloma remain limited. We evaluated a novel therapeutic regimen consisting of carfilzomib, pomalidomide, and dexamethasone (CPD) in an open-label, multicenter, phase 1, dose-escalation study. Patients who relapsed after prior therapy or were refractory to the most recently received therapy were eligible. All patients were refractory to prior lenalidomide. Patients received carfilzomib IV on days 1, 2, 8, 9, 15, and 16 (starting dose of 20/27 mg/m(2)), pomalidomide once daily on days 1 to 21 (4 mg as the initial dose level), and dexamethasone (40 mg oral or IV) on days 1, 8, 15, and 22 of 28-day cycles. The primary objective was to evaluate the safety and determine the maximum tolerated dose (MTD) of the regimen. A total of 32 patients were enrolled. The MTD of the regimen was dose level 1 (carfilzomib 20/27 mg/m(2), pomalidomide 4 mg, dexamethasone 40 mg). Hematologic adverse events (AEs) occurred in ≥60% of all patients, including 11 patients with grade ≥3 anemia. Dyspnea was limited to grade 1/2 in 10 patients. Peripheral neuropathy was uncommon and limited to grade 1/2. Eight patients had dose reductions during therapy, and 7 patients discontinued treatment due to AEs. Two deaths were noted on study due to pneumonia and pulmonary embolism (n = 1 each). The combination of CPD is well-tolerated and highly active in patients with relapsed/refractory multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT01464034.
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Jatin J
authors.initials: JJ
authors.lastname: Shah
authors.affiliation: Clinical Research Unit, University of Pennsylvania Abramson Cancer Center, Philadelphia, PA;
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.affiliation: Indiana University Simon Cancer Center, Indianapolis, IN;
authors.forename: Rafat
authors.initials: R
authors.lastname: Abonour
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA;
authors.forename: Adam D
authors.initials: AD
authors.lastname: Cohen
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Center Research Center, Seattle, WA;
authors.forename: William I
authors.initials: WI
authors.lastname: Bensinger
authors.affiliation: Division of Hematological Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC;
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.affiliation: Bone Marrow and Stem Cell Transplant Center, Winship Cancer Institute, Emory University, Atlanta, GA;
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kaufman
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Colombia University Medical Center, New York, NY;
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lentzsch
authors.affiliation: Clinical Research Unit, University of Pennsylvania Abramson Cancer Center, Philadelphia, PA;
authors.forename: Dan T
authors.initials: DT
authors.lastname: Vogl
authors.affiliation: Criterium, Inc-Academic Myeloma Consortium, Saratoga Springs, NY;
authors.forename: Christina L
authors.initials: CL
authors.lastname: Gomes
authors.affiliation: Criterium, Inc-Academic Myeloma Consortium, Saratoga Springs, NY;
authors.forename: Natalia
authors.initials: N
authors.lastname: Pascucci
authors.affiliation: Division of Biostatistics, Department of Information Sciences, City of Hope, Duarte, CA; and.
authors.forename: David D
authors.initials: DD
authors.lastname: Smith
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Cedars Sinai Samuel Oschin Cancer Center, Los Angeles, CA.
authors.forename: Brian G M
authors.initials: BG
authors.lastname: Durie
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D011014:Pneumonia / Q000139:chemically induced / Q000401:mortality; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000401:mortality; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D013997:Time Factors
chemical_list: D009842:Oligopeptides; D013792:Thalidomide; C524865:carfilzomib; D003907:Dexamethasone; C467566:pomalidomide