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Dr. Torben Plesner - Preliminary safety and efficacy data of daratumumab in combination with lenalidomide and dexamethasone in relapsed or refractory MM

Torben Plesner, MD
Department of Hematology, Vejle Hospital
Vejle, Denmark


Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I

Saturday, December 7, 2013, 5:30 PM-7:30 PM, Hall G (Ernest N. Morial Convention Center)

Torben Plesner, MD1, Tobias Arkenau, MD2*, Henk Lokhorst3, Peter Gimsing, MD, DMSci4*, Jakub Krejcik, MD5*, Charlotte Lemech, MD2*, Monique C. Minnema, MD PhD6, Ulrik Lassen, MD PhD4*, Andrew Cakana, FRCPath, MD7, Nikolai Constantin Brun, MD PhD8, Linda Basse, MD DMSc8*, Antonio Palumbo, MD9 and Paul G. Richardson, MD10

1Dept. of Hematology, Vejle Hospital, Vejle, Denmark
2Sarah Cannon Research Institute, London, United Kingdom
3Department of Hematology, University Medical Center Utrecht, Utrecht, Netherlands
4Rigshospitalet, Copenhagen, Denmark
5Vejle Hospital, Vejle, Denmark
6Hematology, UMC Utrecht, Utrecht, Netherlands
7Johnson & Johnson Pharmaceuticals Research & Development, High Wycombe, United Kingdom
8Genmab A/S, Copenhagen, Denmark
9University of Torino, Azienda Ospedaliero-Universitaria (AOU) S. Giovanni Battista Torino, Torino, Italy
10Dana-Farber Cancer Institute, Boston, MA


Daratumumab (HuMax™-CD38) is a human IgG1κ monoclonal antibody with a broad spectrum of killing activity. It directly targets tumor cells and effectively mediates destruction of CD38-expressing tumor cells via antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, complement-dependent cytotoxicity and apoptosis. In the first-in-human dose-escalation study GEN501 of Daratumumab (DARA) as monotherapy in patients with relapsed or refractory multiple myeloma (MM) the safety profile was acceptable. In doses ≥4mg/kg 42% of the patients achieved a partial response and 25% achieved a minimal response1 according to modified IMWG guidelines2. Targeting MM cells using a direct and indirect antitumor mechanism has shown to be effective3. Combining DARA with lenalidomide (LEN) enhances NK cell-mediated killing of MM cells and is expected to lead to a synergistically higher efficacy as already proven in an ex-vivo setting4. Here, we report the first experience from the GEN503 study combining DARA with LEN and dexamethasone (DEX).

Study design

This is a phase I/II open-label multicenter study of DARA in combination with LEN and DEX including a classic 3 + 3 dose-escalation design. DARA is being administered in doses from 2mg/kg to 16mg/kg weekly for 8 weeks, twice a month for 16 weeks and once a month until disease progression, unmanageable toxicity or up to maximum 24 months. LEN is being administered according to the label and 40mg DEX is being administered once weekly.


The primary objective is to establish the safety profile. The secondary objectives are assessment of efficacy and pharmacokinetics.  


Data from 6 patients (5 male, 1 female) have been collected to date. The study is ongoing. Median age was 63.5 years (48-71). The median number of prior treatment lines was 2.5 (2-4) and median ECOG status was 0.5 (0-1). Preliminary safety data show a manageable safety profile in line with what has previously been reported for LEN. Six adverse events of grade 3 or more (5 events of neutropenia and 1 event of thrombocytopenia) were reported during the first cycle and assessed as related to the combination of DARA with LEN/DEX. Preliminary efficacy evaluation from the first 6 evaluable patients shows that DARA induced a marked reduction in M-protein, yielding a response rate of PR or better. DARA PK data are currently in process. The results presented are based on data analyzed before database lock.


The safety profile has been manageable. DARA induced a marked reduction in M-protein corresponding to all patients achieving a PR or better with 50% achieving VGPR or better. All available data will be updated and presented at the meeting.

1: Lokhorst et al. EHA 2013 abstract #8512

2: Rajkumar et al Blood 2011;117:4691-5

3: Lonial et al. J Clin Oncol 2010;28(15s)

4: van der Veer et al. Haematologica 2011;96(2):284-90

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