PHASE 3 RANDOMIZED STUDY OF DARATUMUMAB + BORTEZOMIB/THALIDOMIDE/DEXAMETHASONE (D-VTD) VERSUS VTD IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PART 1 CASSIOPEIA RESULTS
Author(s): ,
Philippe Moreau
Affiliations:
Hematology, University Hospital Hôtel-Dieu,Nantes,France
,
Michel Attal
Affiliations:
Institut Universitaire du Cancer de Toulouse-Oncopole,Toulouse,France
,
Cyrille Hulin
Affiliations:
Department of Hematology, Hospital Haut Leveque, University Hospital Bordeaux,Bordeaux,France
,
Bertrand Arnulf
Affiliations:
Immuno-Hématologie, Hopital Saint Louis, APHP,Paris,France
,
Karim Belhadj
Affiliations:
Hematology, Hopital Henri Mondor,Creteil,France
,
Lotfi Benboubker
Affiliations:
CHU de Tours, Hôpital de Bretonneau,Tours, Cedex 9,France
,
Marie C. Béné
Affiliations:
Hematology Biology, University Hospital Hôtel Dieu,Nantes,France
,
Annemiek Broijl
Affiliations:
Erasmus MC Cancer Institute,Rotterdam,Netherlands
,
Hélène Caillon
Affiliations:
Biochemistry Laboratory, Hospital of Nantes,Nantes,France
,
Denis Caillot
Affiliations:
CHU Dijon, Hôpital Du Bocage,Dijon,France
,
Jill Corre
Affiliations:
Unite de Genomique du Myelome, IUC-T Oncopole,Toulouse,France
,
Michel Delforge
Affiliations:
Universitaire Ziekenhuizen Leuven,Leuven,Belgium
,
Thomas Dejoie
Affiliations:
Biochemistry Laboratory, Hospital of Nantes,Nantes,France
,
Chantal Doyen
Affiliations:
CHU UCL Namur (site Godinne),Yvoir,Belgium
,
Thierry Facon
Affiliations:
Service des Maladies du Sang, Hôpital Claude Huriez,Lille,France
,
Cécile Sonntag
Affiliations:
Hopital Hautepierre,Strasbourg Cedex,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,Paris,France
,
Kon-Siong Jie
Affiliations:
Zuyderland MC,Sittard,Netherlands
,
Lionel Karlin
Affiliations:
Centre Hospitalier Lyon-Sud Hematologie (HCL),Pierre - Benite Cedex,France
,
Frédérique Kuhnowski
Affiliations:
Institut Curie Paris,Paris,France
,
Jérôme Lambert
Affiliations:
Biostatistical Department, Hôpital Saint Louis,Paris,France
,
Xavier Leleu
Affiliations:
CHU Poitiers - Hôpital la Milétrie,Poitiers,France
,
Pascal Lenain
Affiliations:
CLCC - Centre Henri Becquerel,Rouen Cedex,France
,
Margaret Macro
Affiliations:
Centre Hospitalier Universitaire (CHU) de Caen,Caen,France
,
Frédérique Orsini-Piocelle
Affiliations:
Centre Hospitalier Annecy Genevois,Pringy,France
,
Aurore Perrot
Affiliations:
Hematology Department, University Hospital,Vandoeuvre Les Nancy,France
,
Anne-Marie Stoppa
Affiliations:
Institut Paoli Calmettes,Marseille Cedex 9,France
,
Niels W.C.J. van de Donk
Affiliations:
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology,Amsterdam,Netherlands
,
Soraya Wuilleme
Affiliations:
Hematology Biology, University Hospital Hôtel Dieu,Nantes,France
,
Sonja Zweegman
Affiliations:
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology,Amsterdam,Netherlands
,
Brigitte Kolb
Affiliations:
Hôpital Robert Debré, CHU de Reims,Reims Cedex,France
,
Cyrille Touzeau
Affiliations:
Centre Hospitalier Universitaire,Nantes,France
,
Murielle Roussel
Affiliations:
Institut Universitaire du Cancer de Toulouse-Oncopole,Toulouse,France
,
Mourad Tiab
Affiliations:
CHD Vendée,La Roche sur Yon Cedex 9,France
,
Jean-Pierre Marolleau
Affiliations:
CHU Amiens Sud,Amiens Cedex 1,France
,
Nathalie Meuleman
Affiliations:
Institut Jules Bordet, Université Libre de Bruxelles,Bruxelles,Belgium
,
Marie-Christiane Vekemans
Affiliations:
UCL Saint-Luc,Bruxelles,Belgium
,
Matthijs Westerman
Affiliations:
Northwest Clinics,Alkmaar,Netherlands
,
Saskia K. Klein
Affiliations:
Meander Medical Centre,Amersfoort,Netherlands
,
Mark-David Levin
Affiliations:
Albert Schweitzer Hospital,Dordrecht,Netherlands
,
Martine Escoffre-Barbe
Affiliations:
CHRU Hôpital de Pontchaillou,Rennes Cedex 9,France
,
Jean-Richard Eveillard
Affiliations:
CHRU Brest - Hôpital A. Morvan,BREST Cedex,France
,
Reda Garidi
Affiliations:
Centre Hospitalier,Saint Quentin Cedex,France
,
Tahamtan Ahmadi
Affiliations:
Genmab US, Inc.,Princeton, NJ,United States
,
Sen Zhuang
Affiliations:
Janssen Research & Development,Raritan, NJ,United States
,
Christopher Chiu
Affiliations:
Janssen Research & Development,Spring House, PA,United States
,
Lixia Pei
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
,
Elena Smith
Affiliations:
Janssen Research & Development,High Wycombe,United Kingdom
,
William Deraedt
Affiliations:
Janssen Research & Development,Beerse,Belgium
,
Tobias Kampfenkel
Affiliations:
Janssen Research & Development, LLC,Leiden,Netherlands
,
Jordan Schecter
Affiliations:
Janssen Research & Development,Raritan, NJ,United States
,
Jessica Vermeulen
Affiliations:
Janssen Research & Development, LLC,Leiden,Netherlands
,
Hervé Avet-Loiseau
Affiliations:
Unite de Genomique du Myelome, IUC-T Oncopole,Toulouse,France
Pieter Sonneveld
Affiliations:
Erasmus MC Cancer Institute,Rotterdam,Netherlands
EHA Library. Moreau P. Jun 14, 2019; 267346; S145
Prof. Philippe Moreau
Prof. Philippe Moreau
Contributions
×
Abstract
This abstract is embargoed until Friday, June 14, 08:30 local time.

Abstract: S145

Type: Presidential Symposium

Presentation during EHA24: On Friday, June 14, 2019 from 15:45 - 16:00

Location: Hall 5

Background
VTd is a standard of care for transplant-eligible newly diagnosed multiple myeloma (NDMM) patients. Daratumumab (DARA), a CD38 mAb, significantly reduced the risk of progression or death and improved complete response (CR) and minimal residual disease (MRD)-negative rates in relapsed refractory multiple myeloma or transplant-ineligible NDMM in phase 3 studies.

Aims
We report the primary and final analysis of Part 1 of the CASSIOPEIA trial for NDMM.

Methods
In Part 1, transplant-eligible NDMM patients 18-65 years old were randomized 1:1 to VTd (6 28-day cycles [C; 4 pre-autologous stem cell transplantation {ASCT} induction, 2 post-ASCT consolidation] of V 1.3 mg/m2 SC BIW Week [W] 1-2; T 100 mg PO QD; d 40-80 mg/week PO or IV W 1-4 C 1-2, W 1-3 C 3-6) ± DARA (16 mg/kg IV QW C 1-2, Q2W C 3-6). Melphalan 200 mg/m2 was pre-ASCT therapy. The primary endpoint was the rate of post-consolidation stringent complete response (sCR) assessed at Day 100 post-ASCT. Part 2 (maintenance) is ongoing.

Results

A cohort of 1085 patients (D-VTd, 543; VTd, 542) was randomized. The Day 100 post-ASCT sCR rate was significantly higher for the D-VTd arm versus the VTd arm (28.9% vs 20.3%; P = 0.0010; Table). With 18.8-months median follow-up, progression-free survival (PFS) from first randomization favored D-VTd with a hazard ratio (HR) of 0.47 (95% CI, 0.33-0.67; P <0.0001; Figure). With median PFS not reached in either arm, 18-month PFS rates were 92.7% versus 84.6% for D-VTd versus VTd. Rates of ≥CR, ≥VGPR, and MRD negativity supported sCR results (Table). Overall survival is immature with 46 deaths on study (D-VTd, 14; VTd, 32; HR, 0.43; 95% CI, 0.23-0.80). The most common (≥10%) grade 3/4 treatment-emergent adverse events (D-VTd/VTd) were neutropenia (27.6%/14.7%), lymphopenia (17.0%/9.7%), stomatitis (12.7%/16.4%), and thrombocytopenia (11.0%/7.4%). In the D-VTd arm, infusion-related reactions occurred in 35.4% of patients. 

Conclusion
D-VTd in induction prior to and consolidation after ASCT improved depth of response (sCR, ≥CR, and MRD negativity) and PFS with acceptable safety. The favorable benefit-risk profile supports the use of D-VTd in transplant-eligible NDMM. CASSIOPEIA is the first study to demonstrate the clinical benefit of daratumumab plus standard of care in transplant-eligible NDMM patients.

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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