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PHASE 3 RANDOMIZED STUDY OF DARATUMUMAB + BORTEZOMIB/THALIDOMIDE/DEXAMETHASONE (D-VTD) VERSUS VTD IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PART 1 CASSIOPEIA RESULTS

S145

Moreau, P.1; Attal, M.2; Hulin, C.3; Arnulf, B.4; Belhadj, K.5; Benboubker, L.6; Béné, M. C.7; Broijl, A.8; Caillon, H.9; Caillot, D.10; Corre, J.11; Delforge, M.12; Dejoie, T.9; Doyen, C.13; Facon, T.14; Sonntag, C.15; Garderet, L.16; Jie, K.-S.17; Karlin, L.18; Kuhnowski, F.19; Lambert, J.20; Leleu, X.21; Lenain, P.22; Macro, M.23; Orsini-Piocelle, F.24; Perrot, A.25; Stoppa, A.-M.26; van de Donk, N. W.27; Wuilleme, S.7; Zweegman, S.27; Kolb, B.28; Touzeau, C.29; Roussel, M.2; Tiab, M.30; Marolleau, J.-P.31; Meuleman, N.32; Vekemans, M.-C.33; Westerman, M.34; Klein, S. K.35; Levin, M.-D.36; Escoffre-Barbe, M.37; Eveillard, J.-R.38; Garidi, R.39; Ahmadi, T.40; Zhuang, S.41; Chiu, C.42; Pei, L.41; Vanquickelberghe, V.43; de Boer, C.44; Smith, E.45; Deraedt, W.43; Kampfenkel, T.44; Schecter, J.41; Vermeulen, J.44; Avet-Loiseau, H.11; Sonneveld, P.8

doi: 10.1097/01.HS9.0000558800.37954.72
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1Hematology, University Hospital Hôtel-Dieu, Nantes

2Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse

3Department of Hematology, Hospital Haut Leveque, University Hospital Bordeaux, Bordeaux

4Immuno-Hématologie, Hopital Saint Louis, APHP, Paris

5Hematology, Hopital Henri Mondor, Creteil

6CHU de Tours, Hôpital de Bretonneau, Tours, Cedex 9

7Hematology Biology, University Hospital Hôtel Dieu, Nantes, France

8Erasmus MC Cancer Institute, Rotterdam, Netherlands

9Biochemistry Laboratory, Hospital of Nantes, Nantes

10CHU Dijon, Hôpital Du Bocage, Dijon

11Unite de Genomique du Myelome, IUC-T Oncopole, Toulouse, France

12Universitaire Ziekenhuizen Leuven, Leuven

13CHU UCL Namur (site Godinne), Yvoir, Belgium

14Service des Maladies du Sang, Hôpital Claude Huriez, Lille

15Hopital Hautepierre, Strasbourg Cedex

16Sorbonne 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

17Zuyderland MC, Sittard, Netherlands

18Centre Hospitalier Lyon-Sud Hematologie (HCL), Pierre - Benite Cedex

19Institut Curie Paris

20Biostatistical Department, Hôpital Saint Louis, Paris

21CHU Poitiers - Hôpital la Milétrie, Poitiers

22CLCC - Centre Henri Becquerel, Rouen Cedex

23Centre Hospitalier Universitaire (CHU) de Caen, Caen

24Centre Hospitalier Annecy Genevois, Pringy

25Hematology Department, University Hospital, Vandoeuvre Les Nancy

26Institut Paoli Calmettes, Marseille Cedex 9, France

27Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, Netherlands

28Hôpital Robert Debré, CHU de Reims, Reims Cedex

29Centre Hospitalier Universitaire, Nantes

30CHD Vendée, La Roche sur Yon Cedex 9

31CHU Amiens Sud, Amiens Cedex 1, France

32Institut Jules Bordet, Université Libre de Bruxelles

33UCL Saint-Luc, Bruxelles, Belgium

34Northwest Clinics, Alkmaar

35Meander Medical Centre, Amersfoort

36Albert Schweitzer Hospital, Dordrecht, Netherlands

37CHRU Hôpital de Pontchaillou, Rennes Cedex 9

38CHRU Brest - Hôpital A. Morvan, BREST Cedex,

39Centre Hospitalier, Saint Quentin Cedex, France

40Genmab US, Inc., Princeton, NJ

41Janssen Research & Development, Raritan, NJ

42Janssen Research & Development, Spring House, PA, United States

43Janssen Research & Development, Beerse, Belgium

44Janssen Research & Development, LLC, Leiden, Netherlands

45Janssen Research & Development, High Wycombe, United Kingdom

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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.

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Aims:

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

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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.

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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.

Figure

Figure

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Summary/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.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.