The way that multiple myeloma cells distribute throughout the body can relate to treatment types and disease progression in various ways. Imaging can be a robust source of useful information in these cases.
This article, published in Nature Communications, attempts to address the evolution of multiple myeloma (MM) in whole bone marrow, in order to inform curative strategies. The authors performed spatial-longitudinal whole-exome sequencing, including 140 samples from 24 multiple myeloma patients over 14 years. They tracked resistant clones over time in order to detect the spatiotemporal pathways that are active in MM as treatment goes on. They also demonstrated the effects of combining functional imaging and tumor sequencing to provide a more complete picture of MM’s subclonal evolution.
Left and right iliac crest samples showed a high degree of homogeneity, supporting the idea that a second random biopsy does not usually provide additional information. Frequent unshared mutations were found in paired baseline iliac crest and focal lesion samples. Precursors of resistant disease were found frequently as dominant subclones in focal lesions, suggesting that focal lesions may be a major site of progressed disease.
Other results are also described, including follow-up sampling that supports the existence of a single-cell expansion mechanism in relapsed disease states, with other findings supporting other models and distribution patterns, including alternating spatial clonal dominance and clonal competition.
The authors then describe the way that clinical features relate to these different evolutionary patterns. Although there was not a significant variation between patients in the single-cell expansion group and alternating spatial clonal dominance groups and patients with coexisting subclones, the variation that was found could likely be accounted for by suboptimal treatment responses, which were related to variations in treatment intensity.
The authors conclude that their findings about MM evolution show the need for functional imaging at diagnosis and for assessing treatment response. They especially note that the presence of single cells that can drive relapse, even after long periods, suggests an emphasis on the need for curative therapies to overcome tumor heterogeneity as well as dormancy.
Reference
Rasche, L., Schinke, C., Maura, F., Bauer, M. A., Ashby, C., Deshpande, S., . . . Weinhold, N. (2022). The spatio-temporal evolution of multiple myeloma from baseline to relapse-refractory states. Nat Commun, 13(1), 4517. https://doi.org/10.1038/s41467-022-32145-y
