Practical Considerations for the Use of Daratumumab, a Novel CD38 Monoclonal Antibody, in Myeloma.
Monoclonal antibodies (mAbs) are a recent addition to multiple myeloma (MM) therapies and a number of mAbs directed at myeloma cell surface molecules are in development. Daratumumab is a CD38 mAb that has demonstrated substantial activity and good tolerability in four phase I, phase I/II and phase II studies as monotherapy, as well as in combination with current standard treatments in MM. The positive results obtained in the relapsed/refractory setting in patients with advanced-stage disease and in a small number of patients with newly diagnosed disease provide the rationale for the investigation of the agent in a number of ongoing phase III trials. mAbs are generally better tolerated than conventional chemotherapy; however, their use requires other special considerations. Such factors include those common to all mAbs, namely infusion-related reactions, but also factors that are observed with mAbs used in myeloma, such as interference with response assessment, or factors that are related to CD38 mAbs such as daratumumab, for instance blood typing interference. Our review provides an overview of the results from the daratumumab clinical trials conducted to date, as well as practical management considerations for the use of daratumumab based on our experience with the agent.
Hematology Department, University Hospital Hôtel-Dieu, Place Ricordeau, 44093, Nantes, France. philippe.moreau@chu-nantes.fr.
Philippe
P
Moreau
VU University Medical Center, Amsterdam, The Netherlands.
Niels W C J
NW
van de Donk
University Hospital Navarra, Pamplona, Spain.
Jesus
J
San Miguel
VU University Medical Center, Amsterdam, The Netherlands.
Henk
H
Lokhorst
Karolinska University Hospital Huddinge, Stockholm, Sweden.
Hareth
H
Nahi
Hadassah Medical Center, Jerusalem, Israel.
Dina
D
Ben-Yehuda
University School of Medicine, Bologna, Italy.
Michele
M
Cavo
St James's University Hospital, Leeds, UK.
Gordon
G
Cook
Catholic University of Leuven, Leuven, Belgium.
Michel
M
Delforge
Julius Maximilian University, Würzburg, Germany.
Hermann
H
Einsele
VU University Medical Center, Amsterdam, The Netherlands.
Sonja
S
Zweegman
Wilhelminen hospital, Vienna, Austria.
Heinz
H
Ludwig
Kantonsspital St. Gallen, St. Gallen, Switzerland.
Christoph
C
Driessen
University of Torino, Torino, Italy.
Antonio
A
Palumbo
University Hospital Lille, Lille, France.
Thierry
T
Facon
Vejle Hospital and University of Southern Denmark, Vejle, Denmark.
Torben
T
Plesner
University Athens School of Medicine, Athens, Greece.
Meletios
M
Dimopoulos
University of Giessen, Giessen, Germany.
Pia
P
Sondergeld
Erasmus MC Cancer Insitute, Rotterdam, The Netherlands.
Pieter
P
Sonneveld
University Hospital of Salamanca, Salamanca, Spain.
María-Victoria
MV
Mateos
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D009101:Multiple Myeloma / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C556306:daratumumab; D051997:ADP-ribosyl Cyclase 1