title: 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.
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.).
authors.affiliation: Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Wolschke
authors.forename: Thomas
authors.initials: T
authors.lastname: Stübig
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Stefan
authors.initials: S
authors.lastname: Schönland
authors.forename: Marion
authors.initials: M
authors.lastname: Heinzelmann
authors.forename: York
authors.initials: Y
authors.lastname: Hildebrandt
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
authors.forename: Axel
authors.initials: A
authors.lastname: Zander
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D018450:Disease Progression; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects*; D000077269:Lenalidomide; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000601:surgery*; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D012074:Remission Induction; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D007155:Immunologic Factors; D013792:Thalidomide; D000077269:Lenalidomide