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 language | English (US) |
|---|---|
| Pages (from-to) | 2351-2356 |
| Number of pages | 6 |
| Journal | Leukemia |
| Volume | 27 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2013 |
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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 journal › Article
}
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 -