EFFICACY OF DARATUMUMAB + BORTEZOMIB/THALIDOMIDE/DEXAMETHASONE (D-VTD) IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA BASED ON MINIMAL RESIDUAL DISEASE STATUS: ANALYSIS OF CASSIOPEIA
Author(s): ,
Hervé Avet-Loiseau,
Affiliations:
Unite de Genomique du Myelome, IUC-T Oncopole,Toulouse,France
,
Philippe Moreau
Affiliations:
Hematology, University Hospital Hôtel-Dieu,Nantes,France
,
Vincent H. J. van der Velden
Affiliations:
Department of Immunology,Erasmus MC,Rotterdam,Netherlands
,
Michel Attal
Affiliations:
Institut Universitaire du Cancer de Toulouse-Oncopole,Toulouse,France
,
Cyrille Hulin
Affiliations:
Department of Hematology,Hospital Haut Leveque, University Hospital Bordeaux,Pessac,France
,
Bertrand Arnulf
Affiliations:
Immuno-Hématologie, Hopital Saint Louis, APHP,Paris,France
,
Jill Corre
Affiliations:
Unite de Genomique du Myelome, IUC-T Oncopole,Toulouse,France
,
Laurent Garderet
Affiliations:
Sorbonne Université, INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Team Proliferation and Differentiation of Stem Cells,Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Département d'Hématologie et de Thérapie Cellulaire, Hôpital Pitié Salpetrière, département d'hématologie,Paris,France
,
Lionel Karlin
Affiliations:
Centre Hospitalier Lyon-Sud Hématologie (HCL),Pierre - Bénite Cedex,France
,
Jérôme Lambert
Affiliations:
Biostatistical Department, Hôpital Saint Louis,Paris,France
,
Margaret Macro
Affiliations:
Centre Hospitalier Universitaire (CHU) de Caen,Caen,France
,
Aurore Perrot
Affiliations:
Hematology Department, University Hospital,Vandoeuvre Les Nancy,France
,
Pieter Sonneveld
Affiliations:
Erasmus MC Cancer Institute,Rotterdam,Netherlands
,
Mark-David Levin
Affiliations:
Albert Schweitzer Hospital,Dordrecht,Netherlands
,
Saskia Klein
Affiliations:
Meander Medical Centre,Amersfoort,Netherlands
,
Christopher Chiu
Affiliations:
Janssen Research & Development,Spring House, PA,United States
,
Lixia Pe
Affiliations:
Janssen Research & Development,Raritan, NJ,United States
,
Veronique Vanquickelberghe
Affiliations:
Janssen Research & Development,Beerse,Belgium
,
Carla de Boer
Affiliations:
Janssen Research & Development, LLC,Leiden,Netherlands
,
Tobias Kampfenkel
Affiliations:
Janssen Research & Development, LLC,Leiden,Netherlands
,
Jessica Vermeulen
Affiliations:
Janssen Research & Development, LLC,Leiden,Netherlands
,
Soraya Wuilleme
Affiliations:
Hematology Biology,University Hospital Hôtel Dieu,Nantes,France
Marie C Béné
Affiliations:
Hematology Biology,University Hospital Hôtel Dieu,Nantes,France
EHA Library. Avet-Loiseau H. Jun 15, 2019; 267457; S874
Hervé Avet-Loiseau
Hervé Avet-Loiseau
Contributions
×
Abstract

Abstract: S874

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 16:45 - 17:00

Location: Auditorium

Background
VTd is considered a standard of care for patients with newly diagnosed multiple myeloma (NDMM) who are transplant eligible. The CD38-targeted monoclonal antibody daratumumab (DARA) demonstrated a significant reduction in the risk of progression or death and improvement in stringent complete response (sCR), CR or better (≥CR), and minimal residual disease (MRD)-negative rates when added to VTd in transplant-eligible NDMM patients in the phase 3 CASSIOPEIA study.

Aims
Determine MRD status and its association with progression-free survival (PFS) in transplant-eligible NDMM patients receiving D-VTd versus VTd as pre-transplant induction and post-transplant consolidation in CASSIOPEIA.

Methods
Transplant-eligible NDMM patients were randomized 1:1 to 4 cycles of pre-autologous stem-cell transplant (ASCT) induction and 2 cycles of post-ASCT consolidation with DARA + VTd or VTd. Analyses of MRD were performed on bone marrow aspirates after induction and after consolidation (at Day 100 post-ASCT) for all patients, regardless of response. MRD was assessed primarily by EuroFlow-based multiparametric flow cytometry (MFC) and, based on sample yield, secondarily with next-generation sequencing (NGS; Adaptive clonoSEQ® Assay). Here, we report post-induction and post-consolidation MFC results (10–5 sensitivity threshold) and post-consolidation NGS results (10–6).

Results

A cohort of 1,085 patients received D-VTd (n = 543) or VTd (n = 542). The post-induction MRD-negative rate (MFC, 10–5) was significantly higher for the D-VTd arm versus the VTd arm (34.6% vs 23.1%; P <0.0001; Table). Similarly, post-consolidation MRD-negative rates by MFC (10–5) and NGS (10–6) were significantly higher for patients receiving D-VTd versus VTd (63.7% vs 43.5% and 39.1% vs 22.8%, respectively; P <0.0001 for both analyses; Table). Post-consolidation MRD-negative rates (MFC, 10–5) were consistent across patient subgroups, including ISS stage III or high-risk cytogenetics.

 

Multivariate analyses accounting for treatment arm and MRD negativity (MFC) showed a PFS benefit in patients reaching MRD negativity (HR, 0.31; 95% CI, 0.20-0.50; P <0.0001), and D-VTd showed additional PFS benefit versus VTd alone (HR, 0.48; 95% CI, 0.30-0.78; P = 0.0028). Analysis of MRD based on response (per IMWG criteria) will be presented.

Conclusion
The addition of DARA to VTd during induction and consolidation deepened responses, as demonstrated by significant increases in MRD-negative rates. Deepened post-consolidation responses with D-VTd led to improved outcomes, with MRD negativity associated with prolonged PFS, versus VTd in patients with NDMM who were transplant eligible.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Minimal residual disease (MRD), Monoclonal antibody, Multiple myeloma, Stem cell transplant

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