Postallograft lenalidomide induces strong NK cell-mediated antimyeloma activity and risk for T cell-mediated GvHD

• Verfasst von: Wolschke, Christine [VerfasserIn]
• Verfasst von: Hegenbart, Ute [VerfasserIn]
• Verfasst von: Schönland, Stefan [VerfasserIn]
• Verfasst von: Dreger, Peter [VerfasserIn]
• Titel: Postallograft lenalidomide induces strong NK cell-mediated antimyeloma activity and risk for T cell-mediated GvHD
• Titelzusatz: Results from a phase I/II dose-finding study
• Verf.angabe: Christine Wolschke, Thomas Stübig, Ute Hegenbart, Stefan Schönland, Marion Heinzelmann, York Hildebrandt, Francis Ayuk, Djordje Atanackovic, Peter Dreger, Axel Zander, and Nicolaus Kröger
• Jahr: 2013
• Umfang: 12 S.
• Fussnoten: Available online 17 October 2012 ; Gesehen am 22.07.2021
• Titel Quelle: Enthalten in: Experimental hematology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1999
• Jahr Quelle: 2013
• Band/Heft Quelle: 41(2013), 2, Seite 134-142.e3
• ISSN Quelle: 1873-2399
• DOI: doi:10.1016/j.exphem.2012.10.004
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1764147960

Abstract

Lenalidomide may prevent relapses after allogeneic stem cell transplantation by promoting the immune-mediated graft-versus-tumor effect. We performed a prospective phase I/II study to define the dose-limiting toxicity and the immunologic effects of lenalidomide given early (day 100-180) after allograft for four cycles in patients with multiple myeloma. According to the Fibonacci design, 24 patients with a median age of 53 years were included. Dose-limiting toxicity was organ toxicity owing to graft-versus-host disease, and the maximum tolerable dose was 5 mg. The incidence of graft-versus-host disease after lenalidomide was 38%, occurring after a median of 22 days, and was beside organ toxicity, a leading cause to discontinue the study in 29% of the patients. Immune monitoring revealed a significant increase in peripheral γ-interferon-secreting CD4+ and CD8+ T cells within the first week of lenalidomide treatment followed by a delayed increase in T regulatory cells. Furthermore, natural killer (NK) cells isolated from the peripheral blood of patients evidenced a significantly improved antimyeloma activity after lenalidomide treatment. The immune effect might have contributed to the increased CR rate from 24-42% after lenalidomide treatment because nonresponding patients showed significantly less natural killer and T cell activation. (Study registered under: NCT 00778752.)