Myeloma UK funded research recently published in Leukemia shows that acquisition of new copy number aberrations is associated with relapse and therefore strongly supports the need for repeated molecular analysis at relapse.

Chromosomal changes like copy number aberrations (structural amplifications, gains, or deletions) are a feature of myeloma. However, the relationship between copy number aberrations (CNAs) and myeloma progression has not been established.

The myeloma research team, led by Dr Martin Kaiser at The Institute of Cancer Research, London, analyzed matched diagnosis–relapse tumour pairs for 178 patients to learn about what role copy number aberrations play the progression of myeloma.

The results showed that in 87.1% of tumours relapse was associated with the acquisition of new CNAs. Most of these CNAs were large-scale chromosome changes. The most frequent chromosomal changes associated with relapse were gain or amplification of 1q, del(13q), gain or amplification of 11q and del(17p). Acquisition of gain(1q) at relapse was associated with shorter OS, independent of other risk markers or time of relapse.

The findings also highlighted that CNA acquisition evolution pattern had prognostic value with a branching pattern being significantly associated with reduced overall survival. CNA acquisition evolution patterns differed substantially between myeloma subtypes. Hyperdiploid (HRD) tumours typically evolved in a branching pattern, t(4;14) tumours typically evolved in a linear pattern and t(11;14) tumours had a stable pattern.

This research clearly shows the value of repeat molecular profiling to inform treatment decisions and myeloma patient management. This will become even more important due to the increase in the treatment options at relapse.

Dr Martin Kaiser is the recipient of the Jacqueline Forbes-Nixon Fellowship.