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 journalArticle

62 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 (US)
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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Jakubowiak, A. J., Siegel, D. S., Martin, T., Wang, M., Vij, R., Lonial, S., Trudel, S., Kukreti, V., Bahlis, N., Alsina, M., Chanan-Khan, A., Buadi, F., Reu, F. J., Somlo, G., Zonder, J., Song, K., Stewart, A. K., Stadtmauer, E., Harrison, B. L., ... Jagannath, S. (2013). 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. Leukemia, 27(12), 2351-2356. https://doi.org/10.1038/leu.2013.152