Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials

被引:186
作者
Jagannath, S.
Richardson, P. G.
Sonneveld, P.
Schuster, M. W.
Irwin, D.
Stadtmauer, E. A.
Facon, T.
Harousseau, J-L
Cowan, J. M.
Anderson, K. C.
机构
[1] St Vincents Comprehens Canc Ctr, Dept Med Oncol, New York, NY 10011 USA
[2] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA
[3] Erasmus MC, Dept Hematol, Rotterdam, Netherlands
[4] Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Ctr Lymphoma & Myeloma, New York, NY 10021 USA
[5] Alta Bates Canc Ctr, Bone & Marrow Transplantat Program, Berkeley, CA USA
[6] Univ Penn, Abramson Canc Ctr, Bone Marrow & Stem Cell Transplant Program, Philadelphia, PA 19104 USA
[7] Hosp Claude Huriez, Serv Malad Sang, Lille, France
[8] Hop Hotel Dieu, Dept Hematol, Nantes, France
[9] Tufts New England Med Ctr, Dept Pathol, Boston, MA USA
关键词
bortezomib; chromosome; 13; FISH; metaphase cytogenetics; multiple myeloma; survival;
D O I
10.1038/sj.leu.2404442
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
In multiple myeloma, deletion of chromosome 13 ( del( 13)) is associated with poor prognosis regardless of treatment. This study analyzed the impact of del( 13) status on response and survival following treatment with either bortezomib or high-dose dexamethasone in patients in the SUMMIT and APEX trials. Additionally, matched-pairs subset analyses were conducted of patients with and without del( 13), balanced for age and International Staging System parameters. In both SUMMIT and APEX, prognosis appeared to be poorer in bortezomib-treated patients with del( 13) compared with patients with no del( 13) by metaphase cytogenetics. In the SUMMIT and APEX matched-pairs analysis, response and survival appeared comparable in bortezomib-treated patients with or without del( 13) by metaphase cytogenetics. However, patients with del( 13) receiving dexamethasone in APEX appeared to have markedly decreased survival compared with those without del( 13) by metaphase cytogenetics. These matched-pairs analyses suggest that bortezomib may overcome some of the poor impact of del( 13) as an independent prognostic factor. However, sample sizes were very small; these findings require confirmation from further studies.
引用
收藏
页码:151 / 157
页数:7
相关论文
共 30 条
[1]
Thalidomide and hematopoietic-cell transplantation for multiple myeloma [J].
Barlogie, B ;
Tricot, G ;
Anaissie, E ;
Shaughnessy, J ;
Rasmussen, E ;
van Rhee, F ;
Fassas, A ;
Zangari, M ;
Hollmig, K ;
Pineda-Roman, M ;
Lee, C ;
Talamo, G ;
Thertulien, R ;
Kiwan, E ;
Krishna, S ;
Fox, M ;
Crowley, J .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (10) :1021-1030
[2]
Desikan R, 2000, BLOOD, V95, P4008
[3]
Chromosome 13 abnormalities identified by FISH analysis and serum β2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy [J].
Facon, T ;
Avet-Loiseau, H ;
Guillerm, G ;
Moreau, P ;
Geneviève, F ;
Zandecki, M ;
Laï, JL ;
Leleu, X ;
Jouet, JP ;
Bauters, F ;
Harousseau, JL ;
Bataille, R ;
Mary, JY .
BLOOD, 2001, 97 (06) :1566-1571
[4]
Chromosome 13 deletion/hypodiploidy and prognosis in multiple myeloma patients [J].
Fassas, ABT ;
Tricot, G .
LEUKEMIA & LYMPHOMA, 2004, 45 (06) :1083-1091
[5]
Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma [J].
Fassas, ABT ;
Spencer, T ;
Sawyer, J ;
Zangari, M ;
Lee, CK ;
Anaissie, E ;
Muwalla, F ;
Morris, C ;
Barlogie, B ;
Tricot, G .
BRITISH JOURNAL OF HAEMATOLOGY, 2002, 118 (04) :1041-1047
[6]
Fonseca R, 2002, CANCER RES, V62, P715
[7]
Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and-17p13 in myeloma patients treated with high-dose therapy [J].
Gertz, MA ;
Lacy, MQ ;
Dispenzieri, A ;
Greipp, PR ;
Litzow, MR ;
Henderson, KJ ;
Van Wier, SA ;
Ahmann, GJ ;
Fonseca, R .
BLOOD, 2005, 106 (08) :2837-2840
[8]
International staging system for multiple myeloma [J].
Greipp, PR ;
San Miguel, J ;
Durie, BGM ;
Crowley, JJ ;
Barlogie, B ;
Bladé, J ;
Boccadoro, M ;
Child, JA ;
Harousseau, JL ;
Kyle, RA ;
Lahuerta, JJ ;
Ludwig, H ;
Morgan, G ;
Powles, R ;
Shimizu, K ;
Shustik, C ;
Sonneveld, P ;
Tosi, P ;
Turesson, I ;
Westin, J .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (15) :3412-3420
[9]
Determination of chromosome 13 status in bone marrow cells of patients with multiple myeloma using combined morphologic and fluorescence in situ hybridization analysis [J].
Hardan, I ;
Rothman, R ;
Gelibter, A ;
Cohen, N ;
Shimoni, A ;
Sokolovsky, M ;
Reichart, M ;
Ishoev, G ;
Amariglio, N ;
Rechavi, G ;
Nagler, A ;
Trakhtenbrot, L .
EXPERIMENTAL HEMATOLOGY, 2004, 32 (03) :254-260
[10]
A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma [J].
Jagannath, S ;
Barlogie, B ;
Berenson, J ;
Siegel, D ;
Irwin, D ;
Richardson, PG ;
Niesvizky, R ;
Alexanian, R ;
Limentani, SA ;
Alsina, M ;
Adams, J ;
Kauffman, M ;
Esseltine, DL ;
Schenkein, DP ;
Anderson, KC .
BRITISH JOURNAL OF HAEMATOLOGY, 2004, 127 (02) :165-172