Статья

High Levels of Circulating Tumor Plasma Cells as a Key Hallmark of Aggressive Disease in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma

Luca BertaminiSSD Clinical Trial in Oncoematologia e Mieloma Multiplo, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, ItalyStefania OlivaSSD Clinical Trial in Oncoematologia e Mieloma Multiplo, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, ItalyDelia Rota‐ScalabriniMultidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO – IRCCS, Torino, ItalyLaura ParísDivision of Hematology, ASST Papa Giovanni XXIII, Bergamo, ItalySonia MorèClinica di Ematologia, AOU Ospedali Riuniti di Ancona, Ancona, ItalyPaolo CorradiniHematology and Bone Marrow Transplant Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, University of Milan, Milan, ItalyA LeddaMassimo GentileHematology Unit, AO of Cosenza, Cosenza, ItalyGiovanni De SabbataEmatologia, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, ItalyGiuseppe PietrantuonoHematology and Stem Cell Transplantation Unit, IRCCS Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, ItalyAnna PascarellaUOC Ematologia, Ospedale dell'Angelo, Venezia Mestre, ItalyPatrizia TosiHematology Unit, Infermi Hospital, Rimini, ItalyPaola CurciMilena GilestroSSD Clinical Trial in Oncoematologia e Mieloma Multiplo, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, ItalyAndréa CapraSSD Clinical Trial in Oncoematologia e Mieloma Multiplo, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, ItalyPiero GalieniUOC Ematologia e Terapia cellulare, Ospedale C. e G. Mazzoni, Ascoli Piceno, ItalyFrancesco PisaniHematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, ItalyOmbretta AnnibaliUnit of Hematology, Stem Cell Transplantation, University Campus Bio-Medico, Rome, ItalyFederico MonacoSC Ematologia, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, ItalyAnna Marina LiberatiUniversità degli Studi di Perugia, Azienda Ospedaliera Santa Maria, Terni, ItalySalvatore PalmieriMario LuppiDipartimento di Scienze Mediche e Chirurgiche Materno Infantili e dell'Adulto, UNIMORE, UOC Ematologia, Azienda Ospedaliero-Universitaria di Modena, Modena, ItalyRenato ZambelloDepartment of Medicine (DIMED), Hematology and Clinical Immunology Section, Padova University School of Medicine, Padova, ItalyFrancesca FazioHematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, ItalyAngelo BelottiDepartment of Hematology, ASST Spedali Civili di Brescia, Brescia, ItalyPaola TacchettiIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,” Bologna, ItalyPellegrino MustoDepartment of Emergency and Organ Transplantation, “Aldo Moro” University School of Medicine, Bari, ItalyMario BoccadoroSSD Clinical Trial in Oncoematologia e Mieloma Multiplo, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, ItalyFrancesca GaySSD Clinical Trial in Oncoematologia e Mieloma Multiplo, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy

2022en

ABI

Аннотация

PURPOSE High levels of circulating tumor plasma cells (CTC-high) in patients with multiple myeloma are a marker of aggressive disease. We aimed to confirm the prognostic impact and identify a possible cutoff value of CTC-high for the prediction of progression-free survival (PFS) and overall survival (OS), in the context of concomitant risk features and minimal residual disease (MRD) achievement. METHODS CTC were analyzed at diagnosis with two-tube single-platform flow cytometry (sensitivity 4 × 10 –5 ) in patients enrolled in the multicenter randomized FORTE clinical trial (ClinicalTrials.gov identifier: NCT02203643 ). MRD was assessed by second-generation multiparameter flow cytometry (sensitivity 10 –5 ). We tested different cutoff values in series of multivariate (MV) Cox proportional hazards regression analyses on PFS outcome and selected the value that maximized the Harrell's C-statistic. We analyzed the impact of CTC on PFS and OS in a MV analysis including baseline features and MRD negativity. RESULTS CTC analysis was performed in 401 patients; the median follow-up was 50 months (interquartile range, 45-54 months). There was a modest correlation between the percentage of CTC and bone marrow plasma cells ( r = 0.38). We identified an optimal CTC cutoff of 0.07% (approximately 5 cells/µL, C-index 0.64). In MV analysis, CTC-high versus CTC-low patients had significantly shorter PFS (hazard ratio, 2.61; 95% CI, 1.49 to 2.97, P < .001; 4-year PFS 38% v 69%) and OS (hazard ratio, 2.61; 95% CI, 1.49 to 4.56; P < .001; 4-year OS 68% v 92%). The CTC levels, but not the bone marrow plasma cell levels, affected the outcome. The only factor that reduced the negative impact of CTC-high was the achievement of MRD negativity (interaction P = .039). CONCLUSION In multiple myeloma, increasing levels of CTC above an optimal cutoff represent an easy-to-assess, robust, and independent high-risk factor. The achievement of MRD negativity is the most important factor that modulates their negative prognostic impact.

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Идентификаторы

DOI: 10.1200/jco.21.01393

Цитирования и источники

Цитирований: 2Использованных источников: 0

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