Treatment outcomes in patients with relapsed and refractory multiple myeloma and high-risk cytogenetics receiving single-agent carfilzomib in the PX-171-003-A1 study

A. J. Jakubowiak, D. S. Siegel, T. Martin, M. Wang, R. Vij, S. Lonial, S. Trudel, V. Kukreti, N. Bahlis, M. Alsina, A. Chanan-Khan, F. Buadi, F. J. Reu, G. Somlo, J. Zonder, K. Song, A. K. Stewart, E. Stadtmauer, B. L. Harrison, A. F. WongR. Z. Orlowski, S. Jagannath

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Several cytogenetic abnormalities are associated with poor outcomes in multiple myeloma (MM). We prospectively analyzed the impact of cytogenetic abnormalities on outcomes during the phase 2 PX-171-003-A1 study of single-agent carfilzomib for relapsed and refractory MM. In the response-evaluable population (257/266), fluorescence in situ hybridization (FISH)/conventional cytogenetic profiles were available for 229 patients; 62 (27.1%) had high-risk cytogenetics-del 17p13, t(4;14) or t(14;16) by interphase FISH or deletion 13 or hypodiploidy by metaphase cytogenetics-and 167 (72.9%) had standard-risk profiles. Generally, baseline characteristics were similar between the subgroups, but International Staging System stage III disease was more common in high-vs standard-risk patients (41.9% vs 27.5%) as was Eastern Cooperative Oncology Group performance status 1/2 (85.5% vs 68.3%). Overall response was comparable between the subgroups (25.8% vs 24.6%, respectively; P=0.85), while time-to-event end points showed a trend of shorter duration in high-risk patients, including median duration of response (5.6 months (95% confidence interval (CI) 3.7-7.8) vs 8.3 months (95% CI 5.6-12.3)) and overall survival (9.3 (95% CI 6.5-13.0) vs 19.0 months (95% CI 15.4-NE); P=0.0003). Taken together, these findings demonstrate that single-agent carfilzomib is efficacious and has the potential to at least partially overcome the impact of high-risk cytogenetics in heavily pre-treated patients with MM.

Original languageEnglish
Pages (from-to)2351-2356
Number of pages6
JournalLeukemia
Volume27
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • carfilzomib
  • cytogenetics
  • multiple myeloma
  • proteasome inhibitor
  • refractory
  • relapsed

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