Circulating Tumor Cells for the Staging of Patients With Newly Diagnosed Transplant-Eligible Multiple Myeloma
Juan-Jose Garcés 1 , Maria-Teresa Cedena 2 , Noemi Puig 3 , Leire Burgos 1 , Jose J Perez 3 , Lourdes Cordon 4 , Juan Flores-Montero 5 6 , Luzalba Sanoja-Flores 7 , Maria-Jose Calasanz 1 , Albert Ortiol 8 , María-Jesús Blanchard 9 , Rafael Rios 10 , Jesus Martin 7 , Rafael Martínez-Martinez 11 , Joan Bargay 12 , Anna Sureda 8 13 , Javier de la Rubia 4 14 15 , Miguel-Teodoro Hernandez 16 , Paula Rodriguez-Otero 1 , Javier de la Cruz 2 , Alberto Orfao 5 6 , Maria-Victoria Mateos 3 , Joaquin Martinez-Lopez 2 17 , Juan-Jose Lahuerta 2 , Laura Rosiñol 18 , Joan Blade 18 , Jesus F San-Miguel 1 , Bruno Paiva 1
Purpose: Patients with multiple myeloma (MM) may show patchy bone marrow (BM) infiltration and extramedullary disease. Notwithstanding, quantification of plasma cells (PCs) continues to be performed in BM since the clinical translation of circulating tumor cells (CTCs) remains undefined.
Patients and methods: CTCs were measured in peripheral blood (PB) of 374 patients with newly diagnosed MM enrolled in the GEM2012MENOS65 and GEM2014MAIN trials. Treatment included bortezomib, lenalidomide, and dexamethasone induction followed by autologous transplant, consolidation, and maintenance. Next-generation flow cytometry was used to evaluate CTCs in PB at diagnosis and measurable residual disease (MRD) in BM throughout treatment.
Results: CTCs were detected in 92% (344 of 374) of patients with newly diagnosed MM. The correlation between the percentages of CTCs and BM PCs was modest. Increasing logarithmic percentages of CTCs were associated with inferior progression-free survival (PFS). A cutoff of 0.01% CTCs showed an independent prognostic value (hazard ratio: 2.02; 95% CI, 1.3 to 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 significantly improved risk stratification. Outcomes according to the percentage of CTCs and depth of response to treatment showed that patients with undetectable CTCs had exceptional 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 significant increase in PFS.
Conclusion: Evaluation of CTCs in PB outperformed quantification of BM PCs. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible MM.