FISH Abnormalities (including R-ISS defining and IgH mutations) Are Similar across Race and Ethnicity Among Patients with Multiple Myeloma (except higher rates of t(4:14) in Minorities and 1q Amplifications in Asian/Indians)
Authors: Biran Noa , Johnson Camille , Norden Andrew D , Kumar Roger , Vesole David H. , Berk Seth H. , Fitzgerald Denis B. , Siegel David S , Goldberg Stuart L. 
Published: October 2019

Background: Racial disparities in incidence and prevalence in multiple myeloma (MM) are well known with black (B) individuals having 2-3 fold increased risks compared to white non-Hispanic (WNH) populations. An ECOG review (Baker, Blood 2013) and a Mayo Clinic study (Greenberg, Blood Cancer Journal 2015) found a lower frequency of IgH translocations in B patients (pts). However a Veterans Health Administration study (Blue, BJH 2017) did not identify racial differences by classical karyotype procedures. Paulus (ASH 2016) using the COMMPASS database also failed to identify cytogenetic differences by race or ethnicity among approximately 1000 patients but did identify gene expression profiling , gene copy number variations, and gene single nucleotide variations. Our group presented a single institution review (Velez ASCO 2017) of 482 pts and noted that WNH pts had more IgH rearrangements (similar to Mayo) and t(11;14) than minorities. We sought to extend these observations by reviewing the Cota database containing diagnostic information drawn from 12 cancer centers (85 hematologists-oncologists) within the northeast USA.

Methods: The Cota database contains diagnostic, clinical and outcome information abstracted and enriched from the electronic health records. The database is purely observational and has been de-identified for secondary research purposes. Cytogenetics and FISH studies were performed at various laboratories per physician discretion and not all pts were tested for all genomic abnormalities. Fisher-exact test comparisons were calculated.

Results: The electronic health records of 935 pts with MM diagnosed between January 1, 2012 and May 1, 2017 were reviewed. FISH genomic data on 819 pts obtained at the time of initial diagnosis was available including 581 (71%) WNH, 66 (8%) White Hispanic (H), 138 (17%) B, and 34 (4%) Asian/Indian (AI) pts. 454 (55%) were male with median age at initial presentation of 65 years. Subtypes included IgG kappa NHW: 36%, H: 38% B: 38% AI: 32%; IgG lambda NHW: 23%, H: 18% B: 27% AI: 35%; IgA kappa NHW: 14%, H: 15% B: 9% AI: 6%; kappa light chain NHW: 10%, H: 11% B:12% AI: 21%; IgA lambda NHW: 7%, H: 11% B: 5% AI 6%; lambda light chain NHW: 7%, H: 4% B: 4% AI: 6%; other subtypes all 1% or less. Durie-Salmon stage I, II, III was NHW: 8%, 13%, 78%; H: 6%, 8%, 86%; B: 5%, 9%, 86%; AI: 12%, 0%, 88%. As detailed in the Table, FISH identified abnormalities were similar across race and ethnicity, with the exception of higher rates of t(4:14) in minorities and higher rates of 1q amplifications in Asian/Indians (p<0.02).

Conclusions: Unlike the Mayo/ECOG experiences, but similar to the COMMPASS and Veteran's reports, we found no significant differences in the frequency of IgH translocations. We also noted no differences in R-ISS defining high risk abnormality frequencies by racial or ethnicity groupings. Thus differences in incidence or severity of MM appear unlikely to be explained by genomics at the FISH level.

Table. Table.

Disclosures

Biran: Merck: Research Funding; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; BMS: Research Funding. Norden:Cota Inc: Employment. Siegel:Merck: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Goldberg:COTA Inc.: Employment, Equity Ownership.