Postallograft lenalidomide induces strong NK cell-mediated antimyeloma activity and risk for T cell-mediated GvHD: Results from a phase I/II dose-finding study
Christine Wolschke, Thomas Stübig, Ute Hegenbart, Stefan Schönland, Marion Heinzelmann, York Hildebrandt, Francis Ayuk, Djordje Atanackovic, Peter Dreger, Axel Zander, Nicolaus Kröger, Christine Wolschke, Thomas Stübig, Ute Hegenbart, Stefan Schönland, Marion Heinzelmann, York Hildebrandt, Francis Ayuk, Djordje Atanackovic, Peter Dreger, Axel Zander, Nicolaus Kröger
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.).
Trial registration: ClinicalTrials.gov NCT00778752.
Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Source: PubMed