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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
- Source :
-
Experimental Hematology . Feb2013, Vol. 41 Issue 2, p134-142.e3. 0p. - Publication Year :
- 2013
-
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.) [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0301472X
- Volume :
- 41
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Experimental Hematology
- Publication Type :
- Academic Journal
- Accession number :
- 85397747
- Full Text :
- https://doi.org/10.1016/j.exphem.2012.10.004