Prognostic impact of circulating tumour cells in AL amyloidosis

Circulating tumour cells (CTCs) are less plentiful in patients with newly diagnosed light chain (AL) amyloidosis than in patients with multiple myeloma (MM). Therefore, more sensitive instruments are needed to detect these cells in AL amyloidosis. This is important, since CTCs seem to have a prognostic impact on survival outcomes.

“A high number of CTCs is now considered to be a very unfavourable prognostic factor in patients with MM [1],” explained Dr Ioannis Kostopoulos (University of Athens, Greece). “We wondered whether we can use CTCs as a biomarker in AL amyloidosis.” To investigate this matter, the research team included 218 patients with newly diagnosed AL amyloidosis and prospectively evaluated CTCs with next-generation flow cytometry [2].

Dr Kostopoulos said that the observed number of CTCs was much lower in AL amyloidosis than in MM. “ In the AL amyloidosis population, the median value was 0.00037% CTCs per peripheral blood mononuclear cells (PBMCs),” he stated. More abundant CTCs were associated with higher NTproBNP levels and bone marrow infiltration. The research team noted that there was no association between the number of CTCs and the presence of high-risk cytogenetics. However, patients with a gain of chromosome 1q21 were more likely to have detectable CTC levels. Dr Kostopoulos pointed out that there was no link between CTC levels and haematological or organ response at 1, 3, or 6 months. Nevertheless, CTC level as a continuous variable was an independent prognostic factor for event-free survival (HR 1.29; 95% CI 1.08–1.54; P=0.004) and overall survival (HR 1.44; 95% CI 1.21–1.70; P<0.001). The CTC cut-offs for event-free survival and overall survival were established at ‘level of detection’ and 0.006%, respectively. “These cut-off values could be utilised to refine current prognostic systems,” added Dr Kostopoulos. Finally, patients with detectable CTCs had a 45% reduced probability of achieving an MRD-negative response.

“The differential presence of CTCs has an independent prognostic impact on event-free survival and overall survival in patients with AL amyloidosis,” concluded Dr Kostopoulos. “These results need to be validated in larger studies to verify if the evaluation of CTCs should be part of the routine diagnostic workflow.”

1. Kostopoulos I, et al. J Clin Oncol. 2023;41:708-710.
2. Kostopoulos I, et al. The evaluation of circulating tumour cells as prognostic biomarker in newly diagnosed light chain amyloidosis. S195, EHA2025 Congress, 12–15 June, Milan, Italy.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 18 June 20252 September 2025