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 Ayuketang Ayuk; Djordje Atanackovic; Peter Dreger; Axel Zander; Nicolaus Kröger

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.

Standard

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. / Wolschke, Christine ; Stübig, Thomas; Hegenbart, Ute; Schönland, Stefan; Heinzelmann, Marion; Hildebrandt, York; Ayuketang Ayuk, Francis; Atanackovic, Djordje; Dreger, Peter; Zander, Axel; Kröger, Nicolaus.

In: EXP HEMATOL, Vol. 41, No. 2, 2, 2013, p. 133-134.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wolschke, C , Stübig, T, Hegenbart, U, Schönland, S, Heinzelmann, M, Hildebrandt, Y, Ayuketang Ayuk, F, Atanackovic, D, Dreger, P, Zander, A & Kröger, N 2013, '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.', EXP HEMATOL, vol. 41, no. 2, 2, pp. 133-134. <http://www.ncbi.nlm.nih.gov/pubmed/23085463?dopt=Citation>

APA

Wolschke, C., Stübig, T., Hegenbart, U., Schönland, S., Heinzelmann, M., Hildebrandt, Y., Ayuketang Ayuk, F., Atanackovic, D., Dreger, P., Zander, A., & Kröger, N. (2013). 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. EXP HEMATOL, 41(2), 133-134. [2]. http://www.ncbi.nlm.nih.gov/pubmed/23085463?dopt=Citation

Vancouver

Wolschke C , Stübig T, Hegenbart U, Schönland S, Heinzelmann M, Hildebrandt Y et al. 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. EXP HEMATOL. 2013;41(2):133-134. 2.

Bibtex

@article{242460a3325a4fa69821fec4845df317,

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 ?-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.).",

keywords = "Adult, Humans, Male, Aged, Female, Middle Aged, Prospective Studies, Combined Modality Therapy, Disease Progression, Remission Induction, Transplantation, Homologous, Lymphocyte Count, Lymphocyte Activation/drug effects, *Peripheral Blood Stem Cell Transplantation, Maintenance Chemotherapy, Dose-Response Relationship, Immunologic, Graft vs Host Disease/*etiology/immunology, Graft vs Tumor Effect/*drug effects, Immunologic Factors/administration & dosage/adverse effects/pharmacology/*therapeutic use, Killer Cells, Natural/*drug effects, Multiple Myeloma/drug therapy/immunology/*surgery, T-Lymphocyte Subsets/*drug effects/immunology, T-Lymphocytes, Regulatory/drug effects/immunology, Thalidomide/administration & dosage/adverse effects/*analogs & derivatives/pharmacology/therapeutic use, Transplantation Conditioning, Adult, Humans, Male, Aged, Female, Middle Aged, Prospective Studies, Combined Modality Therapy, Disease Progression, Remission Induction, Transplantation, Homologous, Lymphocyte Count, Lymphocyte Activation/drug effects, *Peripheral Blood Stem Cell Transplantation, Maintenance Chemotherapy, Dose-Response Relationship, Immunologic, Graft vs Host Disease/*etiology/immunology, Graft vs Tumor Effect/*drug effects, Immunologic Factors/administration & dosage/adverse effects/pharmacology/*therapeutic use, Killer Cells, Natural/*drug effects, Multiple Myeloma/drug therapy/immunology/*surgery, T-Lymphocyte Subsets/*drug effects/immunology, T-Lymphocytes, Regulatory/drug effects/immunology, Thalidomide/administration & dosage/adverse effects/*analogs & derivatives/pharmacology/therapeutic use, Transplantation Conditioning",

author = "Christine Wolschke and Thomas St{\"u}big and Ute Hegenbart and Stefan Sch{\"o}nland and Marion Heinzelmann and York Hildebrandt and {Ayuketang Ayuk}, Francis and Djordje Atanackovic and Peter Dreger and Axel Zander and Nicolaus Kr{\"o}ger",

year = "2013",

language = "English",

volume = "41",

pages = "133--134",

journal = "EXP HEMATOL",

issn = "0301-472X",

publisher = "Elsevier Inc.",

number = "2",

}

RIS

TY - JOUR

T1 - 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.

AU - Wolschke, Christine

AU - Stübig, Thomas

AU - Hegenbart, Ute

AU - Schönland, Stefan

AU - Heinzelmann, Marion

AU - Hildebrandt, York

AU - Ayuketang Ayuk, Francis

AU - Atanackovic, Djordje

AU - Dreger, Peter

AU - Zander, Axel

AU - Kröger, Nicolaus

PY - 2013

Y1 - 2013

N2 - 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 ?-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.).

AB - 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 ?-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.).

KW - Adult

KW - Humans

KW - Male

KW - Aged

KW - Female

KW - Middle Aged

KW - Prospective Studies

KW - Combined Modality Therapy

KW - Disease Progression

KW - Remission Induction

KW - Transplantation, Homologous

KW - Lymphocyte Count

KW - Lymphocyte Activation/drug effects

KW - Peripheral Blood Stem Cell Transplantation

KW - Maintenance Chemotherapy

KW - Dose-Response Relationship, Immunologic

KW - Graft vs Host Disease/etiology/immunology

KW - Graft vs Tumor Effect/drug effects

KW - Immunologic Factors/administration & dosage/adverse effects/pharmacology/therapeutic use

KW - Killer Cells, Natural/drug effects

KW - Multiple Myeloma/drug therapy/immunology/surgery

KW - T-Lymphocyte Subsets/drug effects/immunology

KW - T-Lymphocytes, Regulatory/drug effects/immunology

KW - Thalidomide/administration & dosage/adverse effects/analogs & derivatives/pharmacology/therapeutic use

KW - Transplantation Conditioning