Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma

• Published in: Blood 2015-11, Vol.126 (20), p.2284-2290
• Main Authors: Shah, Jatin J., Stadtmauer, Edward A., Abonour, Rafat, Cohen, Adam D., Bensinger, William I., Gasparetto, Cristina, Kaufman, Jonathan L., Lentzsch, Suzanne, Vogl, Dan T., Gomes, Christina L., Pascucci, Natalia, Smith, David D., Orlowski, Robert Z., Durie, BrianG.M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Clinical Trials and Observations; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Multiple Myeloma - pathology; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Pneumonia - chemically induced; Pneumonia - mortality; Pulmonary Embolism - chemically induced; Pulmonary Embolism - mortality; Recurrence; Thalidomide - administration & dosage; Thalidomide - adverse effects; Thalidomide - analogs & derivatives; Time Factors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2015-05-643320

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/m2), 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/m2, 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. •This is the first clinical trial to investigate CPD in multiple myeloma.•Results suggest that the regimen is a well-tolerated and highly active combination for patients with relapsed/refractory multiple myeloma.