The Role of Clonal Evolution on Progression, Blood Parameters, and Response to Therapy in Multiple Myeloma

Abstract

IntroductionA variety of biomarkers are considered for diagnosis (e.g., β2-microgobulin, albumin, or LDH) and prognosis [e.g., cytogenetic aberrations detected by fluorescence in situ hybridization (FISH)] of multiple myeloma (MM). More recently, clonal evolution has been established as key. Little is known on the clinical implications of clonal evolution.MethodsWe performed in-depth analyses of 25 patients with newly diagnosed MM with respect to detailed clinical information analyzing blood samples collected at several time points during follow-up (median follow-up: 3.26 years since first diagnosis). We split our cohort into two subgroups: with and without new FISH clones developing in the course of disease.ResultsEach subgroup showed a characteristic chromosomal profile. Forty-three percent of patients had evidence of appearing new clones. The patients with new clones showed an increased number of translocations affecting chromosomes 14 (78% vs. 33%; p = 0.0805) and 11, and alterations in chromosome 4 (amplifications and translocations). New clones, on the contrary, were characterized by alterations affecting chromosome 17. Subsequent to the development of the new clone, 6 out of 9 patients experienced disease progression compared to 3 out of 12 for patients without new clones. Duration of the therapy applied for the longest time was significantly shorter within the group of patients developing new clones (median: 273 vs. 406.5 days; p = 0.0465).DiscussionWe demonstrated that the development of new clones, carrying large-scale alterations, was associated with inferior disease course and shorter response to therapy, possibly affecting progression-free survival and overall survival as well. Further studies evaluating larger cohorts are necessary for the validation of our results.

clevRvis: visualization techniques for clonal evolution

“…Studying clonal evolution in more detail, a diverse set of analyses can be performed: the model of clonal evolution (linear vs. branched dependent vs. branched independent; of note, neutral and punctuated evolution will be considered special cases of branched and linear evolution) [ 8 , 9 ] can be determined; correlation to blood parameters, therapy resistance, and disease progression investigated [ 10 ]; and patterns characterizing subgroups of patients explored. For example, by detailed analysis of clonal evolution, evidence was found that relapsing BL is associated with the presence of clones, featuring double-hit events in TP53 [ 8 ].…”