Effect of iFISH defined 1q21 amplification/gain in multiple myeloma patients treated on total therapy protocols.

Abstract

8023 Background: The amplification of the proximal 1q21 region has been reported by interphase FISH (iFISH) in about 40% of newly diagnosed patients, and in 70% of MM patients at relapse. We hereby report the prognostic value of 1q21 amplification/gain by iFISH at enrollment in subjects treated on total therapy (TT) 4, 5 and 6 protocols. Methods: TT4 protocol enrolled newly diagnosed patients with LR disease as defined GEP 70 model ≤ 0.66. TT5 was designed for newly diagnosed patients with HR MM.TT6 enrolled previously treated patients with both HR and LR disease. iFISH was performed on bone marrow samples obtained at the time of study enrollment. FISH probes were generated from specific BAC DNA clone for CKS1B gene locus (1q21) gene locus. MM cells were identified post hybridization using isotype specific antibody conjugated with 7-amino-4-methylcoumarin-3-acetic acid (AMCA) to stain Ig-Kappa or Ig-Lambda light chain in cytoplasm (cIg) of MM cells. The iFISH signals in 100 of MM cells were recorded. A 20% cutoff point was used for detection of significant abnormalities i.e. gain of 1q21 (≥ 3 copies). Results: 607 patients were included in this analysis. With a median age of 61 years, 39% had high risk and 88% low risk disease. 1q21 abnormalities were present in 55% of patients at enrollment. 591 patients (97%) received at least one HDT ASCT. The analysis included 382 TT4 patients with a median PFS of 7.2 years and OS not yet reached. 75 patients enrolled on TT5 protocol experienced median PFS of 2.2 years and median OS of 5.6 years.150 TT6 enrolled patients experienced median PFS of 4.1 years and median OS of 7.5 years. Statistically significant difference in PFS (p < 0.0001) and OS (p < 0.0001) was observed between 1q21 defined groups (figure 1). No differences in survival were observed based on the 1q21 copy number > 3. Conclusions: This retrospective analysis clearly showed that 1q21 amplification/gain detected by interphase iFISH in different stages of disease can identify patients with significant shorter progressive free and overall survival even if exposed to total therapy regimens. Clinical trial information: NCT00734877, NCT00869232.