Gaps in CIBMTR Reporting of High Risk Abnormalities in Multiple Myeloma

Background Multiple Myeloma (MM) is a plasma cell neoplasm encompassing a broad clinical spectrum from more indolent to very aggressive, and characterized by heterogeneous genetic makeup.Certain chromosomal abnormalities are noted to be recurrent in MM and confer prognostic and therapeutic significance. Standard risk stratification models such as R-ISS and mSMART include some of those recurrent abnormalities.CIBMTR forms currently track cytogenetic abnormalities identified at the time of initial diagnosis by conventional karyotyping and FISH only. According to CIBMTR requirements abnormalities identified by any other techniques cannot be reported.Beginning 2015 our program implemented routine testing of all plasma cell disorder(PCD) cases by Chromosome Microarray Analysis (CMA) in addition to conventional karyotyping and FISH testing.CMA is a powerful analytic tool for assessment of chromosomal abnormalities. It evaluates the entire genome with high resolution independently of mitotic activity, unlike conventional G-band karyotyping, which is highly important for PCD due to low proliferative index. In addition to detection of copy number changes it allows detection of copy neutral loss of heterozygosity (cnLOH) that cannot be detected by conventional karyotyping or FISH. CMA cannot detect balanced translocations, therefore, it complements but does not substitute FISH, that is required to detect balanced translocations in myeloma cells. Methods We analyzed pathology report of 130 newly diagnosed patients with plasma cells neoplasm, including 82 cases of symptomatic MM and compared results of karyotyping, FISH and CMA tests focusing on identification of high risk abnormalities as defined by mSMART and R-ISS classification. Results Using combination of FISH, karyotyping and CMA we identified significantly higher number of cases with high-risk abnormalities compared to combination of FISH and karyotyping only (Table 1). That indicates that a number of patients with high risk abnormalities were not reported as such to CIBMTR. Summary Our findings suggest that CMA might detect a greater number of patient with high risk cytogenetic abnormalities compared to current reporting standard. Current practice of CIBMTR not accepting CMA results for reporting of cytogenetic abnormalities could skew the perceived risk profile of transplanted patients with multiple myeloma. This discrepancy may underscore the need to reconsider current data acceptance standards to ensure a comprehensive understanding of myeloma patients profile.