Webbläsaren som du använder stöds inte av denna webbplats. Alla versioner av Internet Explorer stöds inte längre, av oss eller Microsoft (läs mer här: * https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Var god och använd en modern webbläsare för att ta del av denna webbplats, som t.ex. nyaste versioner av Edge, Chrome, Firefox eller Safari osv.

Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.

In English

Författare

  • 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
Visa allt

Summary, in English

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 .).

Avdelning/ar

Publiceringsår

2015

Språk

Engelska

Sidor

1207-1219

Publikation/Tidskrift/Serie

New England Journal of Medicine

Volym

373

Issue

13

Dokumenttyp

Artikel i tidskrift

Förlag

Massachusetts Medical Society

Ämne

  • Hematology

Status

Published

Forskningsgrupp

  • Myeloma research group

ISBN/ISSN/Övrigt

  • ISSN: 0028-4793