Skip to main content

29.10.2018 | Original Research | Ausgabe 11/2018 Open Access

Advances in Therapy 11/2018

Pharmacokinetics and Exposure–Response Analyses of Daratumumab in Combination Therapy Regimens for Patients with Multiple Myeloma

Advances in Therapy > Ausgabe 11/2018
Xu Steven Xu, Meletios A. Dimopoulos, Pieter Sonneveld, P. Joy Ho, Andrew Belch, Merav Leiba, Marcelo Capra, David Gomez, Eva Medvedova, Shinsuke Iida, Chang-Ki Min, Jordan Schecter, Richard Jansson, Liping Zhang, Yu-Nien Sun, Pamela L. Clemens
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s12325-018-0815-9) contains supplementary material, which is available to authorized users.

Enhanced digital features

To view enhanced digital features for this article go to https://​doi.​org/​10.​6084/​m9.​figshare.​7165493.



Daratumumab, a human IgG monoclonal antibody targeting CD38, has demonstrated activity as monotherapy and in combination with standard-of-care regimens in multiple myeloma. Population pharmacokinetic analyses were conducted to determine the pharmacokinetics of intravenous daratumumab in combination therapy versus monotherapy, evaluate the effect of patient- and disease-related covariates on drug disposition, and examine the relationships between daratumumab exposure and efficacy/safety outcomes.


Four clinical studies of daratumumab in combination with lenalidomide/dexamethasone (POLLUX and GEN503); bortezomib/dexamethasone (CASTOR); pomalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone, and bortezomib/melphalan/prednisone (EQUULEUS) were included in the analysis. Using various dosing schedules, the majority of patients (684/694) received daratumumab at a dose of 16 mg/kg. In GEN503, daratumumab was administered at a dose of 2 mg/kg (n = 3), 4 mg/kg (n = 3), 8 mg/kg (n = 4), and 16 mg/kg (n = 34). A total of 650 patients in EQUULEUS (n = 128), POLLUX (n = 282), and CASTOR (n = 240) received daratumumab 16 mg/kg. The exposure–efficacy and exposure–safety relationships examined progression-free survival (PFS) and selected adverse events (infusion-related reactions; thrombocytopenia, anemia, neutropenia, lymphopenia, and infections), respectively.


Pharmacokinetic profiles of daratumumab were similar between monotherapy and combination therapy. Covariate analysis identified no clinically important effects on daratumumab exposure, and no dose adjustments were recommended on the basis of these factors. Maximal clinical benefit on PFS was achieved for the majority of patients (approximately 75%) at the 16 mg/kg dose. No apparent relationship was observed between daratumumab exposure and selected adverse events.


These data support the recommended 16 mg/kg dose of daratumumab and the respective dosing schedules in the POLLUX and CASTOR pivotal studies.


Janssen Research & Development.

Unsere Produktempfehlungen

e.Med Interdisziplinär


Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf

Jetzt e.Med zum Sonderpreis bestellen!

Sichern Sie sich jetzt Ihr e.Med-Abo und sparen Sie 50 %!

e.Med Innere Medizin


Mit e.Med Innere Medizin erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Innere Medizin, den Premium-Inhalten der internistischen Fachzeitschriften, inklusive einer gedruckten internistischen Zeitschrift Ihrer Wahl.

Jetzt e.Med zum Sonderpreis bestellen!

Sichern Sie sich jetzt Ihr e.Med-Abo und sparen Sie 50 %!

e.Med Allgemeinmedizin


Mit e.Med Allgemeinmedizin erhalten Sie Zugang zu allen CME-Fortbildungen und Premium-Inhalten der allgemeinmedizinischen Zeitschriften, inklusive einer gedruckten Allgemeinmedizin-Zeitschrift Ihrer Wahl.

Jetzt e.Med zum Sonderpreis bestellen!

Sichern Sie sich jetzt Ihr e.Med-Abo und sparen Sie 50 %!

Über diesen Artikel

Weitere Artikel der Ausgabe 11/2018

Advances in Therapy 11/2018 Zur Ausgabe