Concomitant Deletion of Short Arm (del 1p) and Amplification or Gain (1q21) of Chromosome 1 By Fluorescence in Situ Hybridization (FISH) Is Associated with Poor Clinical Outcome

Introduction- Chromosome 1 abnormalities in multiple myeloma (MM) are increasingly recognized as high risk defined features. While there is robust data on 1q21 gain and amplification (amp), the clinical characteristics and outcome of patients with del 1p is less defined. Novel agents are incorporated into a backbone of multi-agent chemotherapy and tandem autologous stem cell transplantation (ASCT) in successive Total Therapy (TT) protocols for MM patients. We hereby report the prognostic value of del 1p by FISH at enrollment in subjects treated on TT protocols. Methods: (FISH was performed on bone marrow obtained at the time of first visit to our institution or initial diagnosis. FISH probes were generated from specific BAC DNA clones for AHCYL1 gene locus (1p13.3) and CKS1B locus (1q21). 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 myeloma tumor cells. The FISH signals in 100 myeloma cells were recorded. For this analysis, 3 copies of 1q21 are considered as 1q21 gain and ≥ 4 copies as 1q21 amp. A 20% cutoff point was used for detection of significant abnormalities, i.e. del 1p and 1q21 gain and amp. A multivariable logistic regression model was used to examine the combined effects of clinical variables on progression free (PFS) and overall survival (OS). Results- A total of 1133 patients were included in this analysis. The median age was 60 (range 30.2-75), 434 (38.3%) patients were female and 106 (9.4%) were African Americans. ISS stage III disease accounted for 287 (25.3%). GEP70 high-risk was noted in 160/1133 (14.1%) of all patients. Of all patients, 1084 (95.7%) had at least one ASCT and 812 (71.7%) had tandem upfront ASCT. Metaphase cytogenetic abnormalities were noted in 548 (48.4%). While del 1p was detected in 220 (19.4%) patients, 1q21 gain or amplification were observed in 300 (26.5%) and 150 (13.2%) patients, respectively. Isolated 1q21 gain and amplification without del 1p were seen in 235 (20.7%) and 121 (10.7%) patients. Overall, there was enrichment of high-risk features such as ISS stage III disease (5.7% vs 10.9% p=0.049), GEP70 high-risk (8.4% vs 36.8%), GEP 70 subtypes such as MF (4.6% vs 8.2%), MS (10.5% vs 13.6%) and PR (11.3% vs 22.7%) and abnormal cytogenetic abnormalities (45.7% vs 59.5% p= Conclusion: Deletion of short arm of chromosome 1p was observed in 19% of MM patients. Concomitant del 1p with 1q21 gain and /or amp was present in 8% of patients. The PFS and OS of patients with combined del1p/1q21gain abnormalities was significantly worse compared to del 1p alone and 1q21 gain alone and thus identifies a subset of patients with poor clinical outcome. Figure 1 Figure 1. Disclosures Mohan: Medical College of Wisconsin: Current Employment.