The detection of chromosomal aberrations in the main clone appear to have prognostic significance in patients with smoldering multiple myeloma (SMM), according to the results of a study published in Leukemia.

The analysis included 191 patients with SMM, of whom 67 had longitudinal samples. Among the 67 patients, 43 patients had samples after their disease had progressed to multiple myeloma and 24 patients had samples while their status was still considered SMM.

Among the 191 patients with SMM, 114 had subclones. No significant differences in terms of baseline characteristics were seen between the patients who had a subclone and the patients who did not.

The following chromosomal aberrations were found to be associated with an increased risk of disease progression: t(4;14), del 17p13, gain 1q21, del 8p21, and del 13q14. In addition, the increased risk was more pronounced if the chromosomal aberration was harbored in a main clone vs a subclone.


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While the detection of a subclone was not found to be prognostic (hazard ratio [HR], 0.91; 0.58-1.44; P =.7), if a patient had a high-risk chromosomal aberration in the main clone, the detection of additional subclones put these patients at a more pronounced risk (HR, 1.85; 1.01-3.4; P =.048).

In addition, a multivariate analysis showed that in patients with high-risk chromosomal aberrations in the main clone, the detection of a subclone was an independent risk factor for disease progression (HR, 2.34; 1.16-4.71; P =.02).

The analysis also included a previously described group of 139 patients for whom iFISH analysis was done at primary diagnosis and at disease relapse after autologous stem cell transplantation. The time to progression was found to be significantly longer for patients with a de novo chromosomal aberration (with or without evolving subclones) compared with patients who did not have changes or evolving subclones (P =.02).

“Taken together, we show that subclonal CA [chromosomal aberrations] are of prognostic significance, especially in cytogenetically defined high-risk SMM,” the study authors wrote.

Reference

Merz M, Hielscher T, Schult D, et al. Cytogenetic subclone formation and evolution in progressive smoldering multiple myeloma. Leukemia. doi: 10.1038/s41375-019-0634-2