Impact of Genetic Risk Factors on the Outcome of Relapsed/Refractory Multiple Myeloma in the Era of Novel Therapies.
Allan Jiang, Connie Qi, Young Trieu, Donna Reece, Hong Chang. University Health Network, Toronto, Canada
Background: Multiple myeloma (MM), a terminal differentiated B-cell malignancy, is characterized by specific recurrent cytogenetic abnormalities with prognostic implications. We have proposed a genetic based risk stratification model to include chromosome 13q deletion, 17p(p53) deletion, t(4;14), and chromosome 1 abnormalities for MM. However, in the past several years, novel therapies such as proteasome inhibitor bortezomib, and immunomodulatory agent lenalidomide, have improved patients outcome and changed the landscape of management in MM. In the era of novel therapy, the prognostic relevance of those genomic aberrations has not been completely elucidated.
Design: We evaluated a total of 192 relapsed/refractory MM patients treated with bortezomib or 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 13q), del (17p)(p53), t(4;14), del(1p21), and amp (1q21)(CKS1B).
Results: cIg-FISH detected hemizygous 13q deletion in 46/136(34%), 17p(p53) deletion in 22/132 (17%), t(4;14) in 21/131(16%), 1p21 deletion in 33/137 (24%) and 1q21 amplification in 52/145 (36%) cases. There was no significant difference in response to bortezomib or lenalidomide for patients with or without any of the 5 genetic abnormalities tested. However, in bortezomib treated group, only patients with 1q21 amplifications had significantly shorter TTP and OS than those without such abnormalities (median 2.3 vs. 6.0 months; p=0.003; and median 3.8 vs. 12.7 months, p<0.005; respectively). In contrast, in lenalidomide treated group, only patients with 17p(p53) deletions had significantly shorter TTP and OS than those without such abnormalities (median 2.0 vs. 14.3 months; p<0.001; and median 4.7 vs. 31.9 months, p=0.009; respectively). On multi-variant analysis, 1q21 amplification was an independent risk factor for TTP and OS in patients treated with bortezomib whereas del(17p)(p53) predicted a shorter TTP in patients treated with lenalidomide.
Conclusions: Our data suggest that novel therapeutic agents may overcome the adverse effects of del(13q) and t(4;14) but not 1q21 amplification or 17p(p53) deletion in relapsed/refractory MM patients, improved therapeutic strategies are required for these subgroups of patients.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 250, Tuesday Morning