MINIMAL RESIDUAL DISEASE (MRD) BY MULTIPARAMETER FLOW CYTOMETRY (MFC) IN TRANSPLANT ELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (MM): RESULTS FROM THE EMN02/HO95 PHASE 3 TRIAL
Author(s): ,
Stefania Oliva
Affiliations:
Myeloma Unit, Division of Hematology, University of Torino,Torino,Italy
,
Davine Hofste op Bruinink
Affiliations:
Department of Hematology, Erasmus MC Cancer Institute,Rotterdam,Netherlands
,
Lucie Říhová
Affiliations:
Department of Hematology, University Hospital Brno,Brno,Czech Republic
,
Stefano Spada
Affiliations:
Myeloma Unit, Division of Hematology, University of Torino,Torino,Italy
,
Bronno van der Holt
Affiliations:
Department of Hematology, Erasmus MC Cancer Institute, HOVON Data Center,Rotterdam,Netherlands
,
Rossella Troia
Affiliations:
Myeloma Unit, Division of Hematology, University of Torino,Torino,Italy
,
Manuela Gambella
Affiliations:
Myeloma Unit, Division of Hematology, University of Torino,Torino,Italy
,
Lucia Pantani
Affiliations:
Italian Multiple Myeloma Network,GIMEMA,Italy
,
Sara Grammatico
Affiliations:
Italian Multiple Myeloma Network,GIMEMA,Italy
,
Milena Gilestro
Affiliations:
Myeloma Unit, Division of Hematology, University of Torino,Torino,Italy
,
Massimo Offidani
Affiliations:
Italian Multiple Myeloma Network,GIMEMA,Italy
,
Rossella Ribolla
Affiliations:
Italian Multiple Myeloma Network,GIMEMA,Italy
,
Monica Galli
Affiliations:
Italian Multiple Myeloma Network,GIMEMA,Italy
,
Roman Hajek
Affiliations:
Department of Haematooncology, Faculty of Medicine, University of Ostrava and University Hospital of Ostrava,Ostrava,Czech Republic
,
Antonio Palumbo
Affiliations:
Myeloma Unit, Division of Hematology, University of Torino - Currently Takeda Pharmaceuticals Co., Torino,Zurich, Italy,Switzerland
,
Michele Cavo
Affiliations:
Italian Multiple Myeloma Network,GIMEMA,Italy
,
Paola Omedè
Affiliations:
Myeloma Unit, Division of Hematology, University of Torino,Torino,Italy
,
Vincent van der Velden
Affiliations:
Department of Immunology, Erasmus MC, University Medical Center Rotterdam,Rotterdam,Netherlands
,
Mario Boccadoro
Affiliations:
Myeloma Unit, Division of Hematology, University of Torino,Torino,Italy
Pieter Sonneveld
Affiliations:
Department of Hematology, Erasmus MC Cancer Institute,Rotterdam,Netherlands
EHA Library. Oliva S. 06/23/17; 181389; S102
Stefania Oliva
Stefania Oliva
Contributions
Abstract

Abstract: S102

Type: Oral Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 12:00 - 12:15

Location: Hall A

Background
Multiple myeloma (MM) is still an incurable disease and patients may relapse despite achievement of complete remission (CR). Available data show that MRD detection is a sensitive strategy to appropriately measure response in MM patients.

Aims
We evaluated MRD by MFC in patients with newly diagnosed MM enrolled in the EMN02/HO95 phase 3 trial.

Methods
Patients were ≤65 years of age and treatment consisted of Bortezomib-Cyclophosphamide-Dexamethasone (VCD) induction, mobilization and stem cell collection, intensification with Bortezomib-Melphalan-Prednisone (VMP) vs High-Dose-Melphalan (HDM) followed by stem cell transplant, consolidation with Bortezomib-Lenalidomide-Dexamethasone (VRD) vs no consolidation, and Lenalidomide maintenance. MRD was assessed in patients achieving at least a very good partial response (VGPR) before starting maintenance (after HDM, VMP or VRD) and during maintenance every 6-12 months; samples were centralized to 3 European labs. MFC was performed on bone marrow according to Euroflow-based methods (8 colors, 2 tubes) with a sensitivity of 10-5. Quality checks were done to compare sensitivity and to show correlation between protocols (Hofste op Bruinink D, ASH 2016 abstract 2072).

Results
A total of 316 patients could be evaluated before maintenance: median age was 57 years (IQR: 52-62), 18% (57/316) had ISS III and 22% (70/316) had high risk cytogenetic abnormalities defined as presence of either one among del17, t(4;14) or t(14;16); 63% (199/316) had received HDM and 37% (117/316) VMP; thereafter 51% (160/316) had received VRD. After a median follow-up of 30 months from MRD enrolment, 76% (239/316) patients were MRD-negative: 64% (153/239) in the HDM vs 36% (86/239) in the VMP groups. The 3-year PFS was 50% in MRD-positive vs 77% in MRD-negative patients (HR 2.87, 95% CI: 1.75 - 4.72; p<0.001). Subgroup analyses were carried out to assess the risk factors for MRD-positivity according to baseline characteristics and therapies: high risk cytogenetic abnormalities were the most important risk factors (HR 9.87, 95% CI: 4.3 – 22.63; interaction-p=0.001). Finally, 48% of MRD positive patients at pre-maintenance who had a second MRD evaluation after at least 1 year of lenalidomide became MRD-negative.

Conclusion

MRD by MFC is a strong prognostic factor in MM patients receiving intensification with novel agents or transplant; lenalidomide maintenance further improved depth of response; high risk cytogenetic abnormalities are the most important prognostic factors in MRD-positive patients.

Session topic: 13. Myeloma and other monoclonal gammopathies - Biology

Keyword(s): Transplant, Multiple Myeloma, MRD, flow cytometry

Abstract: S102

Type: Oral Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 12:00 - 12:15

Location: Hall A

Background
Multiple myeloma (MM) is still an incurable disease and patients may relapse despite achievement of complete remission (CR). Available data show that MRD detection is a sensitive strategy to appropriately measure response in MM patients.

Aims
We evaluated MRD by MFC in patients with newly diagnosed MM enrolled in the EMN02/HO95 phase 3 trial.

Methods
Patients were ≤65 years of age and treatment consisted of Bortezomib-Cyclophosphamide-Dexamethasone (VCD) induction, mobilization and stem cell collection, intensification with Bortezomib-Melphalan-Prednisone (VMP) vs High-Dose-Melphalan (HDM) followed by stem cell transplant, consolidation with Bortezomib-Lenalidomide-Dexamethasone (VRD) vs no consolidation, and Lenalidomide maintenance. MRD was assessed in patients achieving at least a very good partial response (VGPR) before starting maintenance (after HDM, VMP or VRD) and during maintenance every 6-12 months; samples were centralized to 3 European labs. MFC was performed on bone marrow according to Euroflow-based methods (8 colors, 2 tubes) with a sensitivity of 10-5. Quality checks were done to compare sensitivity and to show correlation between protocols (Hofste op Bruinink D, ASH 2016 abstract 2072).

Results
A total of 316 patients could be evaluated before maintenance: median age was 57 years (IQR: 52-62), 18% (57/316) had ISS III and 22% (70/316) had high risk cytogenetic abnormalities defined as presence of either one among del17, t(4;14) or t(14;16); 63% (199/316) had received HDM and 37% (117/316) VMP; thereafter 51% (160/316) had received VRD. After a median follow-up of 30 months from MRD enrolment, 76% (239/316) patients were MRD-negative: 64% (153/239) in the HDM vs 36% (86/239) in the VMP groups. The 3-year PFS was 50% in MRD-positive vs 77% in MRD-negative patients (HR 2.87, 95% CI: 1.75 - 4.72; p<0.001). Subgroup analyses were carried out to assess the risk factors for MRD-positivity according to baseline characteristics and therapies: high risk cytogenetic abnormalities were the most important risk factors (HR 9.87, 95% CI: 4.3 – 22.63; interaction-p=0.001). Finally, 48% of MRD positive patients at pre-maintenance who had a second MRD evaluation after at least 1 year of lenalidomide became MRD-negative.

Conclusion

MRD by MFC is a strong prognostic factor in MM patients receiving intensification with novel agents or transplant; lenalidomide maintenance further improved depth of response; high risk cytogenetic abnormalities are the most important prognostic factors in MRD-positive patients.

Session topic: 13. Myeloma and other monoclonal gammopathies - Biology

Keyword(s): Transplant, Multiple Myeloma, MRD, flow cytometry

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