In Multiple Myeloma, Minimal Residual Disease (MRD) Is an Early Predictor of Progression and Is Modulated By Maintenance Therapy with Lenalidomide

2014 
Background. Minimal residual disease (MRD) detection by multi-parameter flow cytometry (MFC) and real time quantitative PCR (RQ-PCR) is highly predictive of outcome in multiple myeloma (MM) patients (pts). Less is known on the ability of maintenance therapy to modulate MRD levels. The primary end-point of this study was to monitor MRD during maintenance therapy and to evaluate the impact on outcome. Patients and Methods. In the RV-MM-EMN-441 study (NCT01091831), after induction and consolidation pts received maintenance therapy with either Lenalidomide alone (R) or Lenalidomide-Dexamethasone (RD) until progression. Pts achieving at least very good partial response (VGPR) after induction/consolidation treatment were eligible for the MRD sub-study. MRD analysis was performed on bone marrow (BM) samples at diagnosis, after consolidation, after 3 and 6 courses of maintenance, and thereafter every 6 months until progression. MFC complete remission (CR) was defined by Results. MRD sub-study included 50 pts with a median age of 57 years (range 40-65). After consolidation 34/50 (68%) pts achieved VGPR, 16/48 (32%) achieved CR according to IMWG criteria (Rajkumar et al. Blood 2011). After a median follow-up of 44 months, 22/50 (44%) progressed and 7/50 (14%) deaths were recorded, with a 4-year PFS of 49% and 4-year OS of 87%. In the MFC analysis 19/50 pts (38%) achieved MFC-CR after consolidation, while other additional 7/50 pts (14%) achieved MFC-CR during maintenance. Among pts who achieved MFC–CR ( A molecular marker was identified in 25/50 pts (50%); 4/25 pts (16%) achieved molecular-CR after consolidation, while other additional 3/25 pts (20%) achieved molecular-CR during maintenance. Among pts who achieved molecular–CR ( Conclusions. Lower MRD values, both with MFC and RQ-PCR procedures, predict better outcome. 30% of patients achieved MFC-CR (7/26) or molecular-CR (3/7) during maintenance therapy suggesting that MRD levels can be modified by maintenance. MRD progression anticipates clinical relapse of approximately 8 months. Disclosures Off Label Use: lenalidomide used as off-label. Ferrero: MUNDIPHARMA: Honoraria. Gay: Sanofi: Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Patriarca: Merck Sharp & Dohme: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria. Petrucci: CELGENE: Honoraria; JANSSEN-CILAG: Honoraria; SANOFI: Honoraria; BRISTOL MYERS SQUIBB: Honoraria. Caravita: Celgene: Honoraria. Di Raimondo: CELGENE: Honoraria; JANSSEN-CILAG: Honoraria. Musto: CELGENE: Honoraria; JANSSEN-CILAG: Honoraria. Boccadoro: Sanofi: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Palumbo: Array BioPharma: Honoraria; Onyx Pharmaceuticals: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Genmab A/S: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Honoraria.
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