Kastritis, E. (Efstathios)
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- International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)(2020) Gonzalez-Calle, V. (Veronica); Durie, B. (B.); Hansson, M. (Markus); Ukropec, J. (Jon); Usmani, S.Z. (Saad Z.); Merlini, G. (G.); Zamagni, E. (Elena); Min, C.K. (Chang-Ki); Qi, M. (Ming); Ludwig, H. (Heinz); Hajek, R. (Roman); Mateos, M.V. (María Victoria); De-Larrea, C.F. (Carlos Fernández); Esteves, G. (Graça); Kumar, S. (Shaji); Gozzetti, A. (A.); Morgan, G.J. (Gareth J.); Geraldes, C. (Catarina); Kyriakou, C. (Charalampia); Goldschmidt, H. (Hartmut); Kim, B.S. (Byung-Su); Dimopoulos, M.A. (Meletios A.); Kastritis, E. (Efstathios); Weiss, B.M. (Brendan M.); Fantl, D. (Dorotea); Rajkumar, S.V. (S. Vincent); San-Miguel, J.F. (Jesús F.); Leleu, X. (Xavier); Garderet, L. (Laurent)Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable.
- Impact of minimal residual disease detection by next-generation flow cytometry in multiple myeloma patients with sustained complete remission after frontline therapy(Ovid Technologies (Wolters Kluwer Health), 2019) Kanellias, N. (Nikolaos); Gavriatopoulou, M. (Maria); Kostopoulos, I.V. (Ioannis V.); Ntanasis-Stathopoulos, I. (Ioannis); Tsitsilonis, O.E. (Ourania E.); Migkou, M. (Magdalini); Fotiou, D. (Despina); Spyropoulou-Vlachou, M. (Marilyn); Argyriou, A.T. (Alexandra T.); Paiva, B. (Bruno); Rousakis, P. (Pantelis); Dimopoulos, M.A. (Meletios A.); Ziogas, D.C. (Dimitrios C.); Kastritis, E. (Efstathios); Terpos, E. (Evangelos); Eleutherakis-Papaiakovou, E. (Evangelos); Trougakos, I.P. (Ioannis P.); Papanota, A.M. (Aristea-Maria)Minimal residual disease (MRD) was monitored in 52 patients with sustained CR (≥2 years) after frontline therapy using next-generation flow (NGF) cytometry. 25% of patients initially MRD- reversed to MRD+. 56% of patients in sustained CR were MRD+; 45% at the level of 10−5; 17% at 10−6. All patients who relapsed during follow-up were MRD+ at the latest MRD assessment, including those with ultra-low tumor burden. MRD persistence was associated with specific phenotypic profiles: higher erythroblasts’ and tumor-associated monocytes/macrophages’ predominance in the bone marrow niche. NGF emerges as a suitable method for periodic, reproducible, highly-sensitive MRD-detection at the level of 10−6.
- Evaluation of minimal residual disease using next-generation flow cytometry in patients with AL amyloidosis(Springer Nature, 2018) Kanellias, N. (Nikolaos); Gavriatopoulou, M. (Maria); Kostopoulos, I.V. (Ioannis V.); Tsitsilonis, O.E. (Ourania E.); Migkou, M. (Magdalini); Fotiou, D. (Despina); Roussou, M. (Maria); Paiva, B. (Bruno); Dimopoulos, M.A. (Meletios A.); Ziogas, D.C. (Dimitrios C.); Kastritis, E. (Efstathios); Terpos, E. (Evangelos); Eleutherakis-Papaiakovou, E. (Evangelos); Trougakos, I.P. (Ioannis P.)The treatment of light chain (AL) amyloidosis aims to completely eliminate the toxic light chain production, as assessed by sensitive serum- or urine-based methods such as immunofixation and free light chain (FLCs) quantification. Complete hematologic responses (hemCR) can be achieved in a significant proportion of patients with AL, either with conventional therapies or with high-dose melphalan, and are associated with better overall survival and improved organ function. However, hematologic relapses still occur and organ function may continue to deteriorate due to small residual clones that may lead to disease recurrence and/or may produce very small amounts of toxic light chains which are undetectable by conventional techniques. Next-generation flow cytometry (NGF) is a very sensitive method for the evaluation of minimal residual disease (MRD) and one of the standard methods for the assessment of MRD in patients with multiple myeloma (MM), reflected in the new response assessment criteria2. Patients with MM who are negative for MRD have significantly improved progression-free and overall survival, even among those who have achieved a CR3,4. Such data are sparse in patients with AL amyloidosis, although the presence of MRD may prove a crucial factor for delayed organ response or deterioration of organ function despite conventional hemCR. The aim of the current study was to evaluate feasibility and applicability of MRD by NGF in patients with AL at hemCR.