The Proportion of Clonal Plasma Cells In the Bone Marrow Analyzed by FISH Rather Than Single Chromosomal Abnormalities Predict Progression From Smoldering to Symptomatic Multiple Myeloma
Authors: Neben Kai , Jauch Anna , Hose Dirk , Heiss Christiane , Hielscher Thomas , Bertsch Uta , Seckinger Anja , Hillengass Jens , Raab Marc S. , Ho Anthony D. , Goldschmidt Hartmut 
Published: October 2019

Abstract
Abstract 2950
Smoldering MM (sMM) is a plasma cell disorder defined by the presence of ≥10% plasma cells in bone marrow and/or a monoclonal protein level of ≥3 g/dl in serum without organ damage. The aim of this retrospective study was to analyze whether genomic abnormalities confer prognostic information in patients with sMM who are at high risk of progression into symptomatic MM. By using fluorescent in situ hybridization (FISH), we analyzed the prognostic value of 14 chromosomal abnormalities and hyper-/non-hyperdiploidy (HD and NHD, respectively) in a series of sMM-patients (n=200). In addition, the most frequent chromosomal aberration was used to determine the percentage of clonal plasma cells (cPC) in the bone marrow.
Interphase-FISH-analysis on CD138-enriched plasma cells detected gains of chromosomes 1q21 (31%), 5p15/5q35 (35%), 9q34 (45%), 11q23 (41%), 15q22 (40%), and 19q13 (41%), as well as deletions of chromosomes 8p21 (9%), 13q14 (37%) and 17p13 (7%). Furthermore, the IgH-translocations t(14;16), t(4;14), t(11;14) and IgH-translocations with unknown translocation partner were observed in a frequency of 5%, 10%, 24% and 22%, respectively. The median percentage of cPC was 85.5 (IQR: 62 – 95).
For the entire group, the median follow-up time was 27.2 months (range, 18.2 – 33.5). We analyzed the prognostic impact of each chromosomal aberration on time to progression (TTP). Of all chromosomal abnormalities analyzed, only del(8p21) and the percentage of cPC showed a significant impact on TTP. The TTP at 3 years for patients with del(8p21) was 53% versus 73% for those without (p=0.01). An incremental increase of cPC in the bone marrow by 10% was associated with an elevated relative risk to develop a symptomatic MM of 33% (p<0.001). After adjustment of p-values for multiple testing, only the percentage of cPC showed a statistically significant impact on TTP (p=0.02).
Our results show that FISH-analysis on CD138-enriched plasma cells is a useful technique in the study of sMM, because it allows myelomatous plasma cells to be discriminated from their normal counterparts. In addition, our findings suggest that the proportion of cPC (analyzed by FISH) rather than single chromosomal abnormalities predict progression from sMM to symptomatic MM. FISH-based information can be obtained easily at the time of diagnosis, which would help to establish an individually adapted follow-up strategy.
Aberration yes vs. no N Incidence 3-yr TTP (present vs. absent) Hazard ratio Wald test p-value adjusted del(8p21) 190 9% 53% vs. 73% 2.59 0.1 del(13q14) 200 37% 61% vs. 79% 1.77 0.8 del(17p13) 198 7% 56% vs. 72% 1.95 1 t (4;14) 198 10% 52% vs. 73% 1.68 1 t (11;14) 198 24% 77% vs. 69% 0.51 1 t (14;16) 197 5% 57% vs. 71% 1.59 1 +1q21 197 31% 60% vs. 75% 1.71 1 HD vs. NHD 197 40% 65% vs. 74% 1.67 1 10% increase of cPC 200 – – 1.33 0.02 cPC >95 vs. ≤95% 200 23% vs. 77% 46% vs. 80% 3.84 <0.001

Disclosures:
No relevant conflicts of interest to declare.