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Carfilzomib, pomalidomide, and dexamethasone (CPD) in patients with relapsed and/or refractory multiple myeloma

Jatin J. Shah, Edward A. Stadtmauer, Rafat Abonour, Adam D. Cohen, William I. Bensinger, Cristina Gasparetto, Jonathan L. Kaufman, Suzanne Lentzsch, Dan T. Vogl, Christina L. Gomes, Natalia Pascucci, David D. Smith, Robert Z. Orlowski and Brian G.M. Durie

Key points

  • 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.

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 in an open-label, multicenter, phase 1, dose-escalation study. Patients that 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 intravenously on days 1, 2, 8, 9, 15, and 16 (starting dose of 20/27 mg/m2), pomalidomide once daily on days 1-21 (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). Hematological adverse events occurred in ≥60% of all patients, including eleven patients with grade ≥3 anemia. Dyspnea was limited to grade 1/2 in ten patients. Peripheral neuropathy was uncommon and limited to grade 1/2. Eight patients had dose reductions during therapy, and seven patients discontinued treatment due to adverse events. Two deaths were noted on study due to pneumonia and pulmonary embolism (n=1 each). The combination of carfilzomib, pomalidomide, and dexamethasone is well-tolerated and highly active in patients with RRMM. This study was funded by Onyx Pharmaceuticals, Inc., an Amgen subsidiary, and Celgene Corporation. The trial was registered with www.Clinicaltrials.gov: identifier NCT01464034.

  • Submitted May 4, 2015.
  • Accepted September 8, 2015.