Clinical Significance of CTCs in Staging of Newly Diagnosed Transplant-Eligible Patients With Multiple Myeloma

The assessment of circulating tumor cells (CTCs) in peripheral blood outperformed quantification of bone marrow plasma cells and the discovery of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible multiple myeloma (Journal of Clinical Oncology 2022 Jun 6; JCO2101365.doi:10.1200/JCO.21.01365).

Juan José Garcés, MD, Clinica Universidad de Navarra, Cancer Center Universidad de Navarra (CCUN), Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA), Navarra, Spain and colleagues wrote, “Patients with multiple myeloma (MM) may show patchy bone marrow (BM) infiltration and extramedullary disease," adding, "Notwithstanding, quantification of plasma cells (PCs) continues to be presented in BM since the clinical translation of circulating tumor cells (CTCs) remains undefined.”

The primary objective of this study was to classify the clinical significance of CTCs and optimal cutoffs to stratify patients with newly diagnosed transplant-eligible MM.

In the study, CTCs were measured in peripheral blood (PB) of 374 patients with newly diagnosed MM enrolled in the GEM2012MENOS65 and GEM2014MAIN trials.

The treatments were comprised of bortezomib, lenalidomide, and dexamethasone induction followed by autologous transplant, consolidation, and maintenance. Researchers employed next-generation flow cytometry to evaluate CTCs in PB at diagnosis and measurable residual disease (MRD) in BM throughout treatment.

Research revealed that CTCs were detected in 92% (344 of 374) of patients with newly diagnosed MM. The relationship between the percentages of CTCs and BM PCs was modest. Inferior progression-free survival (PFS) was correlated with escalating logarithmic percentages of CTCs.

A cutoff of 0.01% CTCs indicated an independent prognostic value (hazard ratio: 2.02; 95% CI, 1.3–3.1; P = .001) in multivariable PFS analysis including the International Staging System, lactate dehydrogenase levels, and cytogenetics. The combination of the four prognostic factors substantially enhanced risk stratification. Outcomes according to the percentage of CTCs and depth of response to treatment demonstrated that patients with undetectable CTCs had excellent PFS regardless of complete remission and MRD status. In all other cases with detectable CTCs, only achieving MRD negativity (and not complete remission) demonstrated a statistically considerable rise in PFS.

The authors concluded, “Our data support the inclusion of CTCs into the list of laboratory examinations in [PB] at diagnosis and urge considering its utility to enhance the current stratifying systems for patients with newly diagnosed transplant-eligible MM.”