Low-dose versus High-dose Carfilzomib with Dexamethasone (S1304) in Patients with Relapsed-Refractory Multiple Myeloma
Year: 2020
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Purpose: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits. Patients and Methods: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m2; arm 1) to high-dose carfilzomib (56 mg/m2; arm 2), both with dexamethasone, administered for 12 cycles (11 months) for relapsed and/or refractory multiple myeloma with up to six prior lines of therapy (NCT01903811). The primary endpoint was progression-free survival (PFS), and patients on arm 1 could cross-over to arm 2 after progression on treatment. Results: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (P = 0.113). Also, neither the median PFS [5 months and 8 months, respectively; HR, 1.061; 80% Wald confidence interval (CI), 0.821–1.370; P = 0.384] nor the median overall survival were significantly different (26 and 22 months, respectively; HR, 1.149, 80% Wald CI, 0.841–.571; P = 0.284). Sixteen patients crossed over to arm 2 with a median PFS benefit of 3 months. Certain adverse events (AE) were more frequent in arm 2, including fatigue, thrombocytopenia, and peripheral neuropathy, but there was no significant difference in cardiopulmonary AEs. Conclusions: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m2 dosing of carfilzomib over the 27 mg/m2 dose for the treatment of relapsed and/or refractory multiple myeloma. However, treatment to progression in earlier patient populations with high-dose carfilzomib using different schedules should still be considered as part of the standard of care.
Source: Clinical Cancer Research
Institutions: Mayo Clinic in Florida, Cancer Research And Biostatistics, Columbia University Irving Medical Center, Spectrum Health, Michigan State University, Levine Cancer Institute, University of Pennsylvania, Baylor College of Medicine, Oregon Health & Science University, USC Norris Comprehensive Cancer Center, Kaiser Permanente, Cedars-Sinai Medical Center, The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1204980566, Ozark Health Ventures LLC dba Cancer Research for the Ozarks (CRO), Kaiser Permanente NCI National Community Oncology Research Program, NCORP, G1548551769, National Community Oncology Research Project, The MB-CCOP at Boston Medical Center, G1790576020, ECOG-ACRIN Network Group Operations Center, Northwest NCI Community Oncology Research Program, G2061465891, G2262129301, G2385714708, G2406815399, UCDCCC NCTN U10 Program, G332150848, Proteasome Assembly Chaperones in Sensitivity and Resistance to Proteasome Inhibitors, G3647597407, SWOG Network Group Operations Center of the NCTN, G3748303287, Heartland Cancer Research NCORP, G4289044101, UT MD Anderson Cancer Center Network Lead Academic Participating Site (LAP) UG1, G4768247927, G4874177819, SOUTHWEST ONCOLOGY GROUP CA13612, UT MD Anderson Cancer Center Network Lead Academic Participating Site (LAP), G5671623325, NCI NCTN- Network Lead Academic Participating Site: USC, G5726269583, G594289469, G6078212843, Southwest Oncology Group, G624868453, G629255163, Lead Academic Participating Site for the Development and Conduct of NCTN Trials, G6970698343, Yale Cancer Center NCTN, G712978930, G7222907299, G7342103892, G7451701487, NCI Community Oncology Research Program (NCORP) Community Sites (UG1 Clinical Trial Required), G8231620523, Role of TJP1 in Sensitivity and Resistance to Proteasome Inhibitors in Myeloma, G8490463189, G860041726, Alliance for Clinical Trials in Oncology Operations Center, Montana Cancer Consortium: An Inclusive and Collaborative Approach to Clinical Trial Accrual and Cancer Care Delivery Research across Montana, Idaho and Wyoming, G8852283793, Cancer Center Support Grant, Mayo Clinic Multiple Myeloma SPORE
OpenAlex ID: W3016791437