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2138 Daratumumab in Combination with Dexamethasone in Resistant or Refractory Multiple Myeloma: Primary Results of the IFM2014-04 Trial

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Saturday, December 3, 2016, 5:30 PM-7:30 PM
Hall GH (San Diego Convention Center)

Eileen Mary Boyle, MD, MSc1*, Marie-Odile Petillon, MD1*, Charles Herbaux, MD1*, Johanna Mimouni2*, Xavier Leleu3, Lionel Karlin, MD4*, Chantal Doyen, MD5, Marc Wetterwald, MD, PhD6*, Muriel Roussel, MD7*, Cyrille Hulin8*, Bruno Royer, MD9*, Margaret Macro10*, Philippe Moreau11*, Karel Fostier, MD12*, Mamoun Dib13*, Sabine Brechignac, MD14*, Caroline Bureau15*, Gerald Marit, MD16*, Adrian Tempescul, MD17*, Marie Lorraine Chretien18*, Charles Zarnitsky19*, Cecile Fohrer, MD20*, Aurore Perrot, MD21*, Lotfi Benboubker, MD, PhD22*, Laurent Voillat23*, Jean Valere Malfuson24*, Clara Mariette25*, Mourad Tiab26*, Sophie Rigaudeau27*, Arnaud Jaccard, MD, PhD28*, Anne-Marie Stoppa29, Laure Vincent30*, Jean Claude Eisenmann, MD31*, Laurent Frenzel32*, Bertrand Arnulf, MD33*, Mohamad Mohty, MD, PhD34, Philippe Rodon, MD35, Brigitte Kolb36*, Olivier Decaux, MD, PhD37*, Pascal Godmer38*, David Beauvais1*, Benjamin Carpentier1*, Sarah Bonnet, MD1*, Thomas Longval1*, Mathieu Dewevre1*, Hervé Avet-Loiseau39*, Michel Attal40, Susanna Schraen, PharmD41* and Thierry Facon42

1Service des maladies du sang, Lille University Hospital, Lille, France
2Departement de recherche clinique, Lille University Hospital, Lille, France
4hematology department, Hospices Civils de Lyon, PIERRE BENITE CEDEX, FRA
5Department of Hematology, CHU Dinant Godinne UcL, Yvoir, Belgium
6CHD Dunkerque, Dunkerque, France
7Institut Universitaire du Cancer and University Hospital, Hematology department, Toulouse, France
8Bordeaux Hospital University Center (CHU), Bordeaux, France
9Department of Hematology, University Hospital, Amiens, France
10Hopital Cote De Nacre, Caen Cedex 9, FRA
11Department of Hematology, Nantes University Hospital, Nantes, France
12Uz Brussel, Brussel, BEL
13Hématologie - CHU - Hôpital du Bocage, Angers, France
14Hopital Avicenne, bobigny, France
15Polyclinique Bordeaux Nord Aquitaine, Bordeaux Cedex, FRA
16hematology department, university hospital, Bordeaux, France
17Hematology Department, CHU Brest, Brest, France
18Hématologie Clinique CHU DIJON, Dijon, France
19Hopital J Monod, Brest, France
20HEMATOLOGY, CHU, Strasbourg, FRA
21hematology department, university hospital, Vandoeuvre Les Nancy, France
22Hôpital Bretonneau Service Hématologie et Thérapies Cellulaires, Centre Régional de Cancérologie Henry Kaplan CHRU de Tours, Tours, France
23Centre Hospitalier William Morey, Chalons-sur-Saone, France
24Hôpital d'instruction des armées Percy, Paris Cedex 10, FRA
25Hematology, Grenoble University Hospital, Grenoble, France
26University Hospital, La Roche Sur Yon, France
27Service Hematologie, CHU Andre Mignot, Versailles, France
28Department of Hematology, Centre National de Référence Maladies Rares: Amylose AL et Autres Maladies à Dépôts, CHU Limoges, Limoges, France
29Institut Paoli Calmettes, Marseille, France
30CHU, Montpellier, FRA
31Hematology Department, CH Mulhouse, Mulhouse, France
32Hopital Necker, Paris, FRA
33hematology department, Hôpital Saint Louis, Paris, France
34Department of Haematology, EBMT Paris study office / CEREST-TC / Saint Antoine Hospital, Paris, France
35Centre Hospitalier, Perigueux, France
36Hopital Robert Debre, Reims Cedex, France
37Internal Medicine, University Hospital CHU Rennes, Rennes, France
38Department of Hematology, Hospital, Bretagne atlantique, France
39IUC-Oncopole, Unite de Genomique du Myelome, Toulouse, France
40Institut Universitaire du Cancer-Oncopole, Toulouse, France
41Department of biochemistry, Lille Universiy Hospital, Lille, France
42Service des Maladies du Sang, Hopital Claude Huriez, Lille, France

Introduction: CD38 is highly and uniformly expressed on myeloma cells (1). Daratumumab is a human anti-CD38 IgG1κ monoclonal antibody that has previously shown a favourable safety profile as a single agent in patients with relapsed and refractory (RR) multiple myeloma (MM) (2). This study further assesses the efficacy of Daratumumab in combination with Dexamethasone in heavily pre-treated myeloma patients that are refractory to Lenalidomide, Pomalidomide, and Bortezomib.

Methods: This study is an ongoing, open-label phase II study of Daratumumab in combination with Dexamethasone (NCT02626481). Sixty-four, heavily pretreated Patients were recruited in thirty centres in France and Belgium from November 2015, to receive Daratumumab and Dexamethasone. Daratumumab 16 mg/kg was administered weekly during the first two 28-day cycles, every other week during Cycles three through six, and monthly in Cycle seven and beyond until disease progression or unacceptable toxicity. Patients were all refractory to Lenalidomide (Len), Pomalidomide (Pom) (defined by a progression within 60 days from last drug dosing) and Bortezomib (Bz) (defined by a progression within 6 months from last drug dosing). The primary objective was overall response rate as per the International Myeloma Working Group criteria. A planned safety and efficacy interim analysis was performed after the first 19 patients were enrolled. The last patient was enrolled on the 1stof August 2016.

Results: Sixty-four patients were recruited onto the study. The median age (range) at screening was 61 (30-80). The median number (range) of prior lines of therapy was 6 (2-9). Sixty-seven percent of patient had previously received an autologous stem-cell transplant. At the time of screening, 20% of patients (n=13) had a t(4;14) and 12.5% (n=8) a del(17p).

Planned interim analysis after the first 19 patients were enrolled did not find any unexpected toxicity. Safety and efficacy results (data cut May 15, 2016) of Daratumumab 16 mg/kg are presented here. No patient discontinued treatment due to Treatment Emergent Adverse Event such as infusion related reactions. Ten (15%) patients discontinued treatment due to disease progression after a median of one-cycle. The most common non-haematological TEAEs included infusion related (IRR, n=5, 8%), and fatigue (n=6, 9.3%). All patients with IRRs recovered and continued to receive treatment. Only six (9.5%) patients experienced hyperthermia. Thrombocytopenia and neutropenia were the most frequently reported grade 3 or 4 TEAE (11 and 5% respectively).

Planned interim efficacy assessment showed a response rate (defined as a Partial Response (PR) or greater) in 3/19 patients at the end of the first cycle and 4/19 at the end of the second cycle, and a clinically relevant response (Stable Disease (SD) or greater) at the end of the second cycle for 11 of 19 patients, thus meeting the planed futility criteria and enabling the trial to go forward. As per the 15thof May, among the 40 evaluable patients (that had received at least 2 treatment cycles or progressed within the first) the overall response rate (3) was 25%, with eight (20%) partial responses (PR) and two (5%) very good partial responses (VGPRs) after a median of two cycles (range 1-5). An additional seven patients (17.5%) obtained a Minimal Response (MR) according to the EBMT criteria (4). This is consistent with prior results. Updated results will be presented at the time of ASH.

Conclusions: Daratumumab in combination with Dexamethasone is a safe treatment option with a favourable benefit/risk profile for the treatment of triple relapsed or refractory (Len, Pom and Bz) myeloma patients.

1. Stevenson GT. CD38 as a Therapeutic Target. Mol Med. 2006;12(11–12):345–6.

2. Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24;373(13):1207–19.

3. Kyle R, Rajkumar S. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leuk Off J Leuk Soc Am Leuk Res Fund UK. 2009 Jan;23(1):3–9.

4. Bladé J,et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. Br J Haematol. 1998 Sep;102(5):1115–23.

Disclosures: Boyle: Novartis: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; Janssen: Honoraria. Leleu: Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; TEVA: Membership on an entity's Board of Directors or advisory committees. Hulin: Amgen: Honoraria; Janssen: Honoraria; Bristol: Honoraria; celgene: Honoraria; takeda: Honoraria. Moreau: Novartis: Consultancy, Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Onyx Pharmaceutical: Consultancy, Honoraria. Fohrer: amgen: Consultancy; celgne: Consultancy. Decaux: SIEMENS: Honoraria, Other: supply of free light chain assays , Research Funding; The Binding Site: Other: supply of free light chain assays , Research Funding. Avet-Loiseau: celgene: Consultancy; amgen: Consultancy; janssen: Consultancy; sanofi: Consultancy. Attal: celgene: Consultancy, Research Funding; amgen: Consultancy, Research Funding; janssen: Consultancy, Research Funding; sanofi: Consultancy. Facon: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel and expense, Speakers Bureau.

*signifies non-member of ASH