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, Asher A Chanan Khan, F. Buadi, F. J. Reu, G. Somlo, J. Zonder, K. Song, Alexander Keith Stewart, E. Stadtmauer, B. L. Harrison, A. F. WongR. Z. Orlowski, S. Jagannath

Research output: Contribution to journalArticle

60 Citations (Scopus)

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

Fingerprint

Multiple Myeloma
Cytogenetics
Confidence Intervals
Fluorescence In Situ Hybridization
Chromosome Aberrations
Interphase
Metaphase
carfilzomib
Survival
Population

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

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

In: Leukemia, Vol. 27, No. 12, 12.2013, p. 2351-2356.

Research output: Contribution to journalArticle

Jakubowiak, AJ, Siegel, DS, Martin, T, Wang, M, Vij, R, Lonial, S, Trudel, S, Kukreti, V, Bahlis, N, Alsina, M, Chanan Khan, AA, Buadi, F, Reu, FJ, Somlo, G, Zonder, J, Song, K, Stewart, AK, Stadtmauer, E, Harrison, BL, Wong, AF, Orlowski, RZ & 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, vol. 27, no. 12, pp. 2351-2356. https://doi.org/10.1038/leu.2013.152
Jakubowiak, A. J. ; Siegel, D. S. ; Martin, T. ; Wang, M. ; Vij, R. ; Lonial, S. ; Trudel, S. ; Kukreti, V. ; Bahlis, N. ; Alsina, M. ; Chanan Khan, Asher A ; Buadi, F. ; Reu, F. J. ; Somlo, G. ; Zonder, J. ; Song, K. ; Stewart, Alexander Keith ; Stadtmauer, E. ; Harrison, B. L. ; Wong, A. F. ; Orlowski, R. Z. ; Jagannath, S. / 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. In: Leukemia. 2013 ; Vol. 27, No. 12. pp. 2351-2356.
@article{f0a2d84847f94207875677ec725d1323,
title = "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",
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.",
keywords = "carfilzomib, cytogenetics, multiple myeloma, proteasome inhibitor, refractory, relapsed",
author = "Jakubowiak, {A. J.} and Siegel, {D. S.} and T. Martin and M. Wang and R. Vij and S. Lonial and S. Trudel and V. Kukreti and N. Bahlis and M. Alsina and {Chanan Khan}, {Asher A} and F. Buadi and Reu, {F. J.} and G. Somlo and J. Zonder and K. Song and Stewart, {Alexander Keith} and E. Stadtmauer and Harrison, {B. L.} and Wong, {A. F.} and Orlowski, {R. Z.} and S. Jagannath",
year = "2013",
month = "12",
doi = "10.1038/leu.2013.152",
language = "English (US)",
volume = "27",
pages = "2351--2356",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - 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

AU - Jakubowiak, A. J.

AU - Siegel, D. S.

AU - Martin, T.

AU - Wang, M.

AU - Vij, R.

AU - Lonial, S.

AU - Trudel, S.

AU - Kukreti, V.

AU - Bahlis, N.

AU - Alsina, M.

AU - Chanan Khan, Asher A

AU - Buadi, F.

AU - Reu, F. J.

AU - Somlo, G.

AU - Zonder, J.

AU - Song, K.

AU - Stewart, Alexander Keith

AU - Stadtmauer, E.

AU - Harrison, B. L.

AU - Wong, A. F.

AU - Orlowski, R. Z.

AU - Jagannath, S.

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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.

KW - carfilzomib

KW - cytogenetics

KW - multiple myeloma

KW - proteasome inhibitor

KW - refractory

KW - relapsed

UR - http://www.scopus.com/inward/record.url?scp=84890429728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890429728&partnerID=8YFLogxK

U2 - 10.1038/leu.2013.152

DO - 10.1038/leu.2013.152

M3 - Article

C2 - 23670297

AN - SCOPUS:84890429728

VL - 27

SP - 2351

EP - 2356

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 12

ER -