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Dr. Francesca Gay - Minimal residual disease monitoring during maintenance in MM patients

Francesca Gay, MD
Myeloma Unit, Division of Hematology
University of Torino
Torino, Italy


Program: Oral and Poster Abstracts
Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II

Sunday, December 8, 2013, 6:30 PM-8:30 PM, Hall G (Ernest N. Morial Convention Center)

Alberto Rocci1*, Manuela Gambella1*, Paola Omedè, PhD1*, Daniela Drandi2*, Francesca Gay1*, Francesca Patriarca, MD3*, Federica Cavallo1*, Maria Teresa Petrucci, MD3*, Caravita Tommaso3*, Giulia Benevolo3*, Norbert Pescosta, MD3*, Stefania Oliva1*, Massimo Offidani3*, Vittorio Montefusco3*, Anna Marina Liberati3, Antonietta Pia Falcone, MD3*, Stelvio Ballanti3*, Tonino Spadano, MD3*, Tommasina Guglielmelli3*, Pellegrino Musto, MD3*, Renato Zambello, MD3*, Francesco Di Raimondo, MD3, Marco Ladetto2, Mario Boccadoro, MD1* and Antonio Palumbo, MD1

1Myeloma Unit, Division of Hematology, University of Torino, Torino, Italy
2Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
3Italian Multiple Myeloma Network, GIMEMA, Italy

Background: The quality of response and the residual disease after treatment are important prognostic factors in several hematological diseases including multiple myeloma (MM). Several papers demonstrated that the deeper the response after treatment, the longer the survival. However few data are available on the monitoring of minimal residual disease (MRD) during the maintenance therapy in transplant eligible MM patients. Aims: to evaluate the role of maintenance therapy in reducing MRD and the role of monitoring the response to predict clinical relapse. Patients and Methods: newly diagnosed MM patients enrolled in the RV-MM-EMN-441 trial (NCT01091831) and achieving at least a very good partial response (VGPR) after consolidation were included in the study. Patients received 4 Lenalidomide-Dexamethasone (RD) courses as induction, Cyclophosphamide to mobilize bone marrow stem cells (BMSC) and then were randomized to receive 6 cycles of Cyclophosphamide-Lenalidomide-Dexamethasone (CRD) or Autologous Stem Cell Transplantation (ASCT) with Melphalan 200 mg/m2. All patients received maintenance therapy with Lenalidomide (R) or Lenalidomide-Dexamethasone (RD) until relapse. MRD analysis was performed in a single laboratory (University of Turin, Italy) using flow cytometry according to European Myeloma Network guideline (Rawstron AC, Haematologica 2008). Samples of bone marrow (BM) were collected at diagnosis, after consolidation, after 3 and 6 courses of maintenance and then every 6 months until clinical relapse. The samples were considered MRD +ve if ≥ 0.01% of PC were detected. Immunophenotypic (IF) relapse was defined as an increase of ≥ 25% in the amount of malignant plasma cells in BM compared to the previous determination. Results: Fifty patients (27 female/23 male) with a median age of 57 yrs (40-65) entered the study. According to ISS, 27 patients were stage I, 15 stage II and 8 stage III. Fish risk profile was standard in 31 patients, high in 11 and not available in 8. Twenty-five patients received CRD as consolidation and 25 underwent ASCT. The median follow-up was 28.6 months. After consolidation 16 (32%) patients achieve a complete response (CR) and 34 (68%) a VGPR.  MRD was negative in 19/48 (40%) patients, of which 12 received ASCT (out of 23, 52%) and 7 received CRD (out of 25, 28%). Patients receiving ASCT showed a lower value of residual cells (median 0.08%, range 0 – 1.00) compared to patients receiving CRD (median 0.5%, range 0 – 2.9%, p=0.0134). The lower MRD value was achieved after consolidation in 31 patients (62%), after 3 courses of maintenance in 6 patients (12%) and after 6 or more courses of maintenance in 13 patients (26%). The increase in quality of response was observed primarily in patients receiving CRD: the average amount of residual plasma cells in bone marrow was 71/uL after induction, lowering to 51/uL after 6 and 12 courses of maintenance therapy. Nine patients clinically relapsed after an average time of 25.6 months from the beginning of the therapy and in all patients this was anticipated by immunophenotypic relapse. Conclusions: 1) consolidation therapy with ASCT determines a deeper response compared to CRD; 2) maintenance therapy can improve the quality of response, in particular in patients not receiving ASCT; 3) Immunophenotypic relapse anticipate the clinical relapse. These results suggest the possible role of MRD monitoring to better assess the response to therapy also during maintenance and as marker of early relapse.

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