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Minimal residual disease after transplantation or lenalidomide-based consolidation in myeloma patients: a prospective analysis

Stefania Oliva, Manuela Gambella, Milena Gilestro, Vittorio Emanuele Muccio, Francesca Gay, Daniela Drandi, Simone Ferrero, Roberto Passera, Chiara Pautasso, Annalisa Bernardini, Mariella Genuardi, Francesca Patriarca, Elona Saraci, Maria Teresa Petrucci, Norbert Pescosta, Anna Marina Liberati, Tommaso Caravita, Concetta Conticello, Alberto Rocci, Pellegrino Musto, Mario Boccadoro, Antonio Palumbo and Paola Omedè _

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Oncotarget. 2017; 8:5924-5935. https://doi.org/10.18632/oncotarget.12641

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Abstract

Stefania Oliva1,*, Manuela Gambella1,*, Milena Gilestro1, Vittorio Emanuele Muccio1, Francesca Gay1, Daniela Drandi2, Simone Ferrero2, Roberto Passera3, Chiara Pautasso1, Annalisa Bernardini1, Mariella Genuardi1, Francesca Patriarca4, Elona Saraci1, Maria Teresa Petrucci5, Norbert Pescosta6, Anna Marina Liberati7, Tommaso Caravita8, Concetta Conticello9, Alberto Rocci10, Pellegrino Musto11, Mario Boccadoro1, Antonio Palumbo1, Paola Omedè1

1Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy

2Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy

3Division of Nuclear Medicine, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy

4Azienda Ospedaliera-Universitaria di Udine, DISM Università di Udine, Udine, Italy

5Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy

6Ematologia e Centro TMO, Ospedale Centrale Bolzano, Bozen, Italy

7AO S.Maria di Terni, SC Oncoematologia, Terni, Italy

8UOC Ematologia S.Eugenio ASL RM2 Roma, Rome, Italy

9Divisione di Ematologia, Azienda Policlinico-OVE, Università di Catania, Catania, Italy

10Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK

11Scientific Direction, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy

*Both authors share first authorship of the manuscript

Correspondence to:

Paola Omedè, email: paolaomede@yahoo.com

Keywords: myeloma, MRD, ASO-RQ-PCR, novel agents, flow cytometry

Received: June 11, 2016    Accepted: September 21, 2016    Published: October 13, 2016

ABSTRACT

We analyzed 50 patients who achieved at least a very good partial response in the RV-MM-EMN-441 study. Patients received consolidation with autologous stem-cell transplantation (ASCT) or cyclophosphamide-lenalidomide-dexamethasone (CRD), followed by Lenalidomide-based maintenance. We assessed minimal residual disease (MRD) by multi-parameter flow cytometry (MFC) and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) after consolidation, after 3 and 6 courses of maintenance, and thereafter every 6 months until progression. By MFC analysis, 19/50 patients achieved complete response (CR) after consolidation, and 7 additional patients during maintenance. A molecular marker was identified in 25/50 patients, 4/25 achieved molecular-CR after consolidation, and 3 additional patients during maintenance. A lower MRD value by MFC was found in ASCT patients compared with CRD patients (p=0.0134). Tumor burden reduction was different in patients with high-risk vs standard-risk cytogenetics (3.4 vs 5.2, ln-MFC; 3 vs 6 ln-PCR, respectively) and in patients who relapsed vs those who did not (4 vs 5, ln-MFC; 4.4 vs 7.8 ln-PCR). MRD progression anticipated clinical relapse by a median of 9 months while biochemical relapse by a median of 4 months. MRD allows the identification of a low-risk group, independently of response, and a better characterization of the activity of treatments.


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