Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy

• Published in: Leukemia Vol. 28; no. 7; pp. 1529 - 1536
• Main Authors: Berenson, J R, Hilger, J D, Yellin, O, Dichmann, R, Patel-Donnelly, D, Boccia, R V, Bessudo, A, Stampleman, L, Gravenor, D, Eshaghian, S, Nassir, Y, Swift, R A, Vescio, R A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2014; Nature Publishing Group
• Subjects: 692/699/67/1990/804; 692/700/565/1436/1437; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bone cancer; Boronic Acids - administration & dosage; Boronic Acids - therapeutic use; Bortezomib; Cancer; Cancer Research; Care and treatment; Carfilzomib; Critical Care Medicine; Dosage and administration; Drug dosages; Drug Substitution; Drug therapy; Female; Hematology; Humans; Intensive; Internal Medicine; Leukemia; Male; Medical research; Medicine; Medicine & Public Health; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Multiple Myeloma - pathology; Neoplasm Staging; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Oligopeptides - drug effects; Oncology; original-article; Patients; Pyrazines - administration & dosage; Pyrazines - therapeutic use; Treatment Outcome; Los Angeles California; United States > US; West Hollywood California; relapsed; refractory; multiple myeloma; proteasome inhibitor; bortezomib; carfilzomib
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2014.27

In this open-label, intra-patient phase I/II trial, bortezomib was replaced with carfilzomib (escalated from 20 to 45 mg/m 2 on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle) for multiple myeloma (MM) patients who progressed while on or within 12 weeks of receiving a bortezomib-containing combination regimen. Study objectives included determination of the maximum tolerated dose (MTD), overall response rate (ORR), clinical benefit rate (CBR), time to progression, time to response, duration of response, progression-free survival and overall survival (OS). Of 38 registered patients, 37 were treated and evaluable for efficacy and safety. Thirty-one carfilzomib-based regimens using 14 different drug combinations were tested. One regimen (carfilzomib (45 mg/m 2 ), ascorbic acid (1000 mg) and cyclophosphamide (2.2 mg/kg)) reached MTD. ORR and CBR were 43.2 and 62.2%, respectively. Median progression-free survival, time to progression and OS were 8.3, 9.9 and 15.8 months, respectively. Hematologic adverse events (AEs; ⩾grade 3) included lymphopenia (35.1%), thrombocytopenia (24.3%), anemia (10.8%) and neutropenia (10.8%). Nonhematologic AEs (⩾grade 3) included fever (5.4%) and hypokalemia (5.4%). These results demonstrate that replacing bortezomib with carfilzomib is safe and can be effective for MM patients failing bortezomib-containing combination regimens. This trial was registered at http://www.clinicaltrials.gov (#NCT01365559).