Publication details
Prognostic impact of unfavorable cytogenetic abnormalities in multiple myeloma patients treated by bortezomib (velcade)
| Authors | |
|---|---|
| Year of publication | 2007 |
| Type | Article in Proceedings |
| Conference | Hematologica/The Hematology Journal |
| MU Faculty or unit | |
| Citation | |
| Field | Genetics and molecular biology |
| Keywords | multiple myeloma; 1q21 amplifiaction; Velcade; fluorescence in situ hybridisation; DNA probe |
| Description | i) Introduction: The aim of this study is to investigate if Bortezomib (Velcade) is able to antagonize the impact of negative cytogenetic prognostic markers. We have focused on four chromosomal aberrations known as negative prognostic factors in multiple myeloma (MM) treated by conventional or myeloablastive treatment: deletion of RB gene (13q14), deletion of p53 (17p13), amplification of CKS1B gene (1q21) and translocation t(4;14). ii) Material and Methods: We have identified monotypic plasma cells and studied chromosomal aberrations by cytoplasmic light-chain fluorescence in situ hybridization (cIg-FISH) technique. Up-to-date group of 18 patients (pts.) has following characteristic: 67% of men, median age 62,5 years (44,4-77,9). 50% (9 pts.) were in stage IIIA, 28% (5 pts.) in IIA and 22% (4 pts.) in IA. 61% (11 pts.) were in first relapse, 22% (4 pts.) were in second relapse. The others 17% (3 pts.) were in third relapse. Treatment with Velcade based regimens was continued for up to 8 cycles in 66 % pts. (12/18). ii) Preliminary results: Cytogenetic findings: Deletion of RB gene was found in 8/16 (50%) pts., t(4;14) in 8/15 (53%) pts., deletion of p53 gene in 7/15 (47%) cases and amplification of CKS1B gene in 10/15 pts. (66%). Overall Response (OR) was 39% (0% CR, 11% VGPR, 28% PR). OR was not higher in pts. with cytogenetic findings for all aberration types except t(4;14): OR was 38% vs. 38% for pts. with vs. without deletion of RB gene; 63% vs. 14% for t(4;14) (p=0,240); 29% vs. 50% for deletion of p53 and 40% vs. 40% for amplification of CKS1B. Further, Velcade based therapy showed comparable TTP, DOR and OS in pts. with or without cytogenetic aberations including t(4;14). iv) Preliminary conclusions: We have found no significant difference when compared positivity vs. negativity of each cytogenetic aberration (including t(4;14)) for OR, TTP, DOR, PFS, and OS. This should have been caused by small size of our sample. It is possible that Velcade antagonizes the negative prognostic value of studied cytogenetic findings in MM. Supported by Myeloma Basic Research Centre Brno MU (LC 06027) and by grant from Ministry of Educations MSM0021622415. |
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