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Clinical and immunohistochemical features associated with a response to bortezomib in patients with multiple myeloma.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2009 Jan 15; Vol. 15 (2), pp. 714-22. - Publication Year :
- 2009
-
Abstract
- Purpose: Multiple myeloma is an incurable disease with heterogeneous clinical behavior. Bortezomib has offered some patients with relapsed and refractory disease an opportunity for prolonged survival. However, there remains a paucity of data in patients treated with bortezomib that accurately delineates and identifies such patients. This information is crucial to guide management.<br />Experimental Design: In this study, we aimed to identify the patients most likely to respond to bortezomib salvage therapy. We analyzed the baseline clinical variables and profiled the baseline expression of a broad range of immunohistochemical markers of cell cycle activity, apoptosis, and angiogenesis in a large cohort of multiply relapsed myeloma patients recruited to one of two prospective multicentre trials assessing the efficacy of bortezomib salvage therapy.<br />Results: Using the European Group for Bone Marrow Transplantation criteria, response (complete or partial) to bortezomib salvage therapy was associated with a previous history of complete response to alternative antimyeloma treatment. Patients who expressed cyclin D1 were more likely to achieve a response. In contrast, patients who expressed p16(INK4A), cytoplasmic p53, and the highest intensity of Bcl-2 staining had a poor response. Patients who achieved a response to bortezomib and those patients who expressed cyclin D1 at baseline showed a significant survival advantage. Patients who expressed FGFR3, a poor prognostic marker, responded equally well and had similar outcomes with bortezomib compared with FGFR3-negative patients.<br />Conclusions: Baseline clinical variables and selective immunohistochemical markers expressed by patients may be used effectively to identify patients that are most likely to achieve a meaningful clinical response to bortezomib salvage therapy.
- Subjects :
- Adult
Aged
Bortezomib
Cell Cycle
Cohort Studies
Cyclin D1 biosynthesis
Cyclin-Dependent Kinase Inhibitor p16 biosynthesis
Female
Humans
Male
Middle Aged
Prognosis
Proto-Oncogene Proteins c-bcl-2 biosynthesis
Treatment Outcome
Tumor Suppressor Protein p53 biosynthesis
Antineoplastic Agents therapeutic use
Boronic Acids therapeutic use
Immunohistochemistry methods
Multiple Myeloma drug therapy
Pyrazines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 15
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 19147779
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-08-1022