Cytogenetic Testing in Newly Diagnosed Multiple Myeloma: Real World Evidence on Clinical Features and Adverse Outcomes for High Risk Groups.

BACKGROUND

The International Myeloma Society/International Myeloma Working Group (IMS-IMWG) recently redefined high-risk multiple myeloma (MM), specifying that gain(1q) confers high risk only when co-occurring with monoallelic del(1p), whilst immunoglobulin heavy chain (IgH) translocations (t[4;14], t[14;16], t[14;20]) are considered high risk only when accompanied by gain(1q) or del(1p).

METHODS

Data from 5927 newly diagnosed MM (NDMM) patients in the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) were analyzed. Fluorescence in situ hybridization (FISH) data were available for 3397 (57%) patients. High-risk cytogenetic abnormalities (HRCA) included t(4;14), t(14;16), del(17p), and gain(1q). Clinical characteristics and outcomes were compared by the number of HRCA present.

RESULTS

Patients with multiple HRCA more frequently presented with anemia, thrombocytopenia, hypercalcemia, greater bone marrow plasma cell burden, elevated lactate dehydrogenase, higher β2-microglobulin levels, and IgA paraprotein secretion. Increasing HRCA burden was associated with significantly shorter progression-free survival (PFS) and overall survival (OS). Although overall response rates to first-line therapies were similar across groups, the duration of response declined with increasing HRCA number. Each HRCA independently conferred poorer outcomes compared with no HRCA, with del(17p) associated with the shortest PFS and OS. The addition of another HRCA did not significantly alter outcomes in del(17p) patients.

CONCLUSION

The cumulative burden of high-risk cytogenetic abnormalities predicts inferior survival in NDMM, underscoring the need for refined risk stratification and tailored therapeutic strategies.