Impact of Chromosome 1 Abnormalities on Outcome among Patients with Refractory/Relapsed Multiple Myeloma Treated with Lenalidomide Plus Dexamethasone
C Qi, Y Trieu, C Chen, D Reece, H Chang. University of Toronto, Toronto, Canada
Background: Lenalidomide is an oral immunomodulatory drug that has clinical activity especially in combination with dexamethasone in relapsed or refractory multiple myeloma (MM). We have reported that lenalidomide is active in relapsed/refractory MM patients with genetic risk factors including chromosome 13q deletions and t(4;14) but not 17p(p53) deletions. However, it is unclear whether chromosome 1 abnormalities (1p loss or 1q gains), which are adverse prognostic factors in MM, influence the outcome of lenalidomide treated relapsed/refractory MM patients.
Design: We evaluated 142 relapsed/refractory MM patients treated with lenalidomide plus dexamethasone and correlated response, survival and genomic status detected by interphase cytoplasmic fluorescence in situ hybridization (cIg-FISH). CIg-FISH was performed on clonal plasma cells from MM bone marrow aspirates with probes to detect del (17p)(p53), del(1p21), and amp (1q21)(CKS1B).
Results: 119 (84%) patients had an objective response to lenalidomide with median time to progression (TTP) and overall survival (OS) of 11.0 and 28.2 months, respectively. Of 142 patients, a total of 110 bone marrow samples were evaluable by cIg-FISH. cIg-FISH detected hemizygous 17p(p53) deletion in 12/88 (13.6%), 1p21 deletions in 24/95 (19%) and 1q21 amplification in 38/99 (38%) cases. There was no significant difference in response to lenalidomide for patients with or without 17p(p53) deletions, 1p21 deletions or 1q21(CKS1B) amplifications. However, patients with 1p21 deletions or 17p(p53) deletions had significantly shorter TTP than those without such abnormalities (median 4.6 vs. 13.9 months; p=0.013; and median 2.1 vs. 12.0 months, p<0.001; respectively). The OS was also shorter in patients with 1p21 or 17p(p53) deletions, but did not reach statistical significance. In contrast, patients with and without 1q21(CKS1B) amplifications had comparable survival outcomes.
Conclusions: Our data suggest that chromosome 1p21 and 17p(p53) deletions had an adverse impact on the outcome of patients with relapsed/refractory MM receiving lenalidomide plus dexamethasone, improved therapeutic strategies are required for this subgroup of patients.
Monday, March 22, 2010 1:00 PM
Platform Session: Section B, Monday Afternoon