dc.contributor.author | Luo, MM | |
dc.contributor.author | Usmani, SZ | |
dc.contributor.author | Mateos, M-V | |
dc.contributor.author | Nahi, H | |
dc.contributor.author | Chari, A | |
dc.contributor.author | San-Miguel, J | |
dc.contributor.author | Touzeau, C | |
dc.contributor.author | Suzuki, K | |
dc.contributor.author | Kaiser, M | |
dc.contributor.author | Carson, R | |
dc.contributor.author | Heuck, C | |
dc.contributor.author | Qi, M | |
dc.contributor.author | Zhou, H | |
dc.contributor.author | Sun, Y-N | |
dc.contributor.author | Parasrampuria, DA | |
dc.date.accessioned | 2021-01-28T15:38:13Z | |
dc.date.available | 2021-01-28T15:38:13Z | |
dc.date.issued | 2020-11-03 | |
dc.identifier.citation | Journal of clinical pharmacology, 2020 | |
dc.identifier.issn | 0091-2700 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4331 | |
dc.identifier.eissn | 1552-4604 | |
dc.identifier.doi | 10.1002/jcph.1771 | |
dc.description.abstract | We report the population pharmacokinetic (PK) and exposure-response analyses of a novel subcutaneous formulation of daratumumab (DARA) using data from 3 DARA subcutaneous monotherapy studies (PAVO Part 2, MMY1008, COLUMBA) and 1 combination therapy study (PLEIADES). Results were based on 5159 PK samples from 742 patients (DARA 1800 mg subcutaneously, n = 487 [monotherapy, n = 288; combination therapy, n = 199]; DARA 16 mg/kg intravenously, n = 255 [all monotherapy, in COLUMBA]; age, 33-92 years; weight, 28.6-147.6 kg). Subcutaneous and intravenous DARA monotherapies were administered once every week for cycles 1-2, once every 2 weeks for cycles 3-6, and once every 4 weeks thereafter (1 cycle is 28 days). The subcutaneous DARA combination therapy was administered with the adaptation of corresponding standard-of-care regimens. PK samples were collected between cycle 1 and cycle 12. Among monotherapy studies, throughout the treatment period, subcutaneous DARA provided similar/slightly higher trough concentrations (Ctrough ) versus intravenous DARA, with lower maximum concentrations and smaller peak-to-trough fluctuations. The PK profile was consistent between subcutaneous DARA monotherapy and combination therapies. The exposure-response relationship between daratumumab PK and efficacy or safety end points was similar for subcutaneous and intravenous DARA. Although the ≤65-kg subgroup reported a higher incidence of neutropenia, no relationship was found between the incidence of neutropenia and exposure, which was attributed, in part, to the preexisting imbalance in neutropenia between subcutaneous DARA (45.5%) and intravenous DARA (19%) in patients ≤50 kg. A flat relationship was observed between body weight and any grade and at least grade 3 infections. The results support the DARA 1800-mg subcutaneous flat dose as an alternative to the approved intravenous DARA 16 mg/kg. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0 | |
dc.title | Exposure-Response and Population Pharmacokinetic Analyses of a Novel Subcutaneous Formulation of Daratumumab Administered to Multiple Myeloma Patients. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-10-05 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1002/jcph.1771 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc/4.0 | |
rioxxterms.licenseref.startdate | 2020-11-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of clinical pharmacology | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Myeloma Group | |
icr.researchteam | Myeloma Group | |
dc.contributor.icrauthor | Kaiser, Martin | |