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

// Stefania Oliva 1, * , Manuela Gambella 1, * , Milena Gilestro 1 , Vittorio Emanuele Muccio 1 , Francesca Gay 1 , Daniela Drandi 2 , Simone Ferrero 2 , Roberto Passera 3 , Chiara Pautasso 1 , Annalisa Bernardini 1 , Mariella Genuardi 1 , Francesca Patriarca 4 , Elona Saraci 1 , Maria Teresa Petrucci 5 , Norbert Pescosta 6 , Anna Marina Liberati 7 , Tommaso Caravita 8 , Concetta Conticello 9 , Alberto Rocci 10 , Pellegrino Musto 11 , Mario Boccadoro 1 , Antonio Palumbo 1 , Paola Omede 1 1 Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Citta della Salute e della Scienza di Torino, Torino, Italy 2 Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy 3 Division of Nuclear Medicine, University of Torino, Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino, Torino, Italy 4 Azienda Ospedaliera-Universitaria di Udine, DISM Universita di Udine, Udine, Italy 5 Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy 6 Ematologia e Centro TMO, Ospedale Centrale Bolzano, Bozen, Italy 7 AO S.Maria di Terni, SC Oncoematologia, Terni, Italy 8 UOC Ematologia S.Eugenio ASL RM2 Roma, Rome, Italy 9 Divisione di Ematologia, Azienda Policlinico-OVE, Universita di Catania, Catania, Italy 10 Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK 11 Scientific Direction, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy * Both authors share first authorship of the manuscript Correspondence to: Paola Omede, 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.