Do the "new drugs" antagonize the impact of unfavourable cytogenetic markers in multiple myeloma?
| Authors | |
|---|---|
| Year of publication | 2007 |
| Type | Article in Proceedings |
| Conference | Blood reviews |
| MU Faculty or unit | |
| Citation | |
| Field | Genetics and molecular biology |
| Keywords | multiple myeloma; cIg FISH; velcade; thalidomide |
| Description | Background In our study, we have concentrated on four aberrations in multiple myeloma (MM) malignant plasma cells: deletions of tumor suppressor genes RB (locus 13q14) and p53 (17q13), translocation involving IGH gene t(4;14), and actually focused amplification of CKS1B gene in 1q21 locus. All of these aberrations are known as negative prognostic factors in patients (pts) treated by conventional therapy or stem cell transplantation. Aims The aim of this study is to show if these selected aberrations act as negative prognostic factors also in patients treated by Velcade or by thalidomide, new drugs used in relapsed patients. Methods We have an increasing group of (recently 42) MM patients. Overall clinical characteristics of the patients at the start of treatment: Average age 63.7 years (SD = 9.4), 57 % (24) of men. 12 % (5/42 pts) were in stage IA, 26 % (11/42 pts) were in stage IIA, 60 % (25/42 pts) were in stage IIIA and 2 % (1 patient) was in stage IIIB. 69 % (29/42 pts) were in first relapse, 24 % (10/42 pts) were in second relapse and the other 7 % (3/42 pts) were in third relapse. 85 % (36/42) pts received at least four cycles of therapy. 64 % (27/42) pts reached overall response (OR) during the follow up (average follow up was 11.0 months, SD = 5.3 months). For identification of malignant plasma cells in bone marrow samples, we use cytoplasmic immunoglobulin (cIg) labeling methodology (Ahmann et al. 1998). This method allows us to identify simultaneously monotypic plasma cells by monoclonal antibody fluorescence (anti-kappa or anti-lambda) and to detect chromosomal abnormalities by FISH (cIg-FISH). Results Cytogenetic findings: Deletion of RB gene was found in 57 % (21/37) of successfully examined patients, deletion of p53 gene was in 53 % (17/32) pts, translocation t(4;14) was in 61 % (22/36) pts and amplification of 1q21 was in 65 % (22/34) pts. Statistical comparison of clinical response in patients with or without each aberration: We have found no significant difference when compared overall survival (OS), time to progression (TTP), progression free survival (PFS), duration of response (DOR) and overall response in subgroups of patients with and without of any selected aberration. Summary/Conclusions In our group of patients, no one of monitored aberrations seems to have any impact, neither positive nor negative, on efficiency of used treatment. It is possible that new drugs, Velcade and thalidomide, antagonize the impact of cytogenetic negative prognostic factors in relapsed patients with MM. However, we will continue in this research to reach larger data set to confirm or disconfirm our results. If this data will be confirmed on larger group of patients, it looks necessary to find other chromosomal abnormalities, relevant for prediction of the prognosis in these patients. |
| Related projects: |