Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. A More COMPLETE Picture of Revascularization in STEMI

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Partial Oral Therapy for Osteomyelitis and Endocarditis. Reply

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Effects of Serelaxin in Patients with Acute Heart Failure

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Application of High-Sensitivity Troponin in Suspected Myocardial Infarction

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Cell-free DNA in newly diagnosed patients with glioblastoma - a clinical prospective feasibility study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Withdrawal: Identification of tumor antigens among the HLA peptidomes of glioblastoma tumors and plasma

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Actively personalized vaccination trial for newly diagnosed glioblastoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Henk M Lokhorst
  • Torben Plesner
  • Jacob P Laubach
  • Hareth Nahi
  • Peter Gimsing
  • Markus Hansson
  • Monique C Minnema
  • Ulrik Lassen
  • Jakub Krejcik
  • Antonio Palumbo
  • Niels W C J van de Donk
  • Tahamtan Ahmadi
  • Imran Khan
  • Clarissa M Uhlar
  • Jianping Wang
  • A Kate Sasser
  • Nedjad Losic
  • Steen Lisby
  • Linda Basse
  • Nikolai Brun
  • Paul G Richardson
View graph of relations

BACKGROUND: Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy.

METHODS: In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics.

RESULTS: No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥ 5% of patients) were pneumonia and thrombocytopenia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months.

CONCLUSIONS: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288.).

Original languageEnglish
JournalThe New England journal of medicine
Volume373
Issue number13
Pages (from-to)1207-19
Number of pages13
ISSN0028-4793
DOIs
Publication statusPublished - 24 Sep 2015

    Research areas

  • Adult, Aged, Antibodies, Monoclonal, Antigens, CD38, Antineoplastic Agents, Disease-Free Survival, Dose-Response Relationship, Drug, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Multiple Myeloma, Pneumonia, Thrombocytopenia

ID: 46178331