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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 [Exp Hematol] 2013 Feb; Vol. 41 (2), pp. 134-142.e3. Date of Electronic Publication: 2012 Oct 17. - 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.).<br /> (Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Combined Modality Therapy
Disease Progression
Dose-Response Relationship, Immunologic
Female
Graft vs Host Disease immunology
Humans
Immunologic Factors administration & dosage
Immunologic Factors adverse effects
Immunologic Factors pharmacology
Lenalidomide
Lymphocyte Activation drug effects
Lymphocyte Count
Maintenance Chemotherapy
Male
Middle Aged
Multiple Myeloma drug therapy
Multiple Myeloma immunology
Prospective Studies
Remission Induction
T-Lymphocyte Subsets immunology
T-Lymphocytes, Regulatory drug effects
T-Lymphocytes, Regulatory immunology
Thalidomide administration & dosage
Thalidomide adverse effects
Thalidomide pharmacology
Thalidomide therapeutic use
Transplantation Conditioning
Transplantation, Homologous
Graft vs Host Disease etiology
Graft vs Tumor Effect drug effects
Immunologic Factors therapeutic use
Killer Cells, Natural drug effects
Multiple Myeloma surgery
Peripheral Blood Stem Cell Transplantation
T-Lymphocyte Subsets drug effects
Thalidomide analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2399
- Volume :
- 41
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental hematology
- Publication Type :
- Academic Journal
- Accession number :
- 23085463
- Full Text :
- https://doi.org/10.1016/j.exphem.2012.10.004