Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory 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, Brian G M Durie

Research output: Contribution to journalArticle

131 Citations (Scopus)

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/m2), pomalidomide once daily on days 1 to 21 (4mg 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 20/27mg/m2, pomalidomide 4 mg, dexamethasone 40 mg). Hematologic adverse events (AEs) occurred in ≥60%of all patients, including11patients 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 (n51each).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.

Original languageEnglish (US)
Pages (from-to)2284-2290
Number of pages7
JournalBlood
Volume126
Issue number20
DOIs
StatePublished - Nov 12 2015

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Refractory materials
Dexamethasone
Patient treatment
Maximum Tolerated Dose
Labels
Multiple Myeloma
Therapeutics
carfilzomib
pomalidomide
Peripheral Nervous System Diseases
Pulmonary Embolism
Dyspnea
Anemia
Pneumonia
Safety

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Shah, J. J., Stadtmauer, E. A., Abonour, R., Cohen, A. D., Bensinger, W. I., Gasparetto, C., ... Durie, B. G. M. (2015). Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood, 126(20), 2284-2290. https://doi.org/10.1182/blood-2015-05-643320

Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. / 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, Brian G M.

In: Blood, Vol. 126, No. 20, 12.11.2015, p. 2284-2290.

Research output: Contribution to journalArticle

Shah, JJ, Stadtmauer, EA, Abonour, R, Cohen, AD, Bensinger, WI, Gasparetto, C, Kaufman, JL, Lentzsch, S, Vogl, DT, Gomes, CL, Pascucci, N, Smith, DD, Orlowski, RZ & Durie, BGM 2015, 'Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma', Blood, vol. 126, no. 20, pp. 2284-2290. https://doi.org/10.1182/blood-2015-05-643320
Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C et al. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015 Nov 12;126(20):2284-2290. https://doi.org/10.1182/blood-2015-05-643320
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, Brian G M. / Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. In: Blood. 2015 ; Vol. 126, No. 20. pp. 2284-2290.
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