Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease.

Autor:	Koshy AG; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Kim HT; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA., Liegel J; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Arnason J; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Ho VT; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA., Antin JH; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA., Joyce R; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Cutler C; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA., Gooptu M; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA., Nikiforow S; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA., Logan EK; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Elavalakanar P; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Narcis M; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Stroopinsky D; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Avigan ZM; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Boussi L; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Stephenson S; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA., El Banna H; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA., Bindal P; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Cheloni G; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Avigan DE; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA., Soiffer RJ; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA., Rosenblatt J; Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2023 Jun 15; Vol. 141 (24), pp. 2932-2943.
DOI:	10.1182/blood.2022019107
Abstrakt:	Steroid-refractory chronic graft-versus-host disease (cGVHD) after allogeneic transplant remains a significant cause of morbidity and mortality. Abatacept is a selective costimulation modulator, used for the treatment of rheumatologic diseases, and was recently the first drug to be approved by the US Food and Drug Administration for the prophylaxis of acute graft-versus-host disease. We conducted a phase 2 study to evaluate the efficacy of abatacept in steroid-refractory cGVHD. The overall response rate was 58%, seen in 21 out of 36 patients, with all responders achieving a partial response. Abatacept was well tolerated with few serious infectious complications. Immune correlative studies showed a decrease in interleukin -1α (IL-1α), IL-21, and tumor necrosis factor α as well as decreased programmed cell death protein 1 expression by CD4+ T cells in all patients after treatment with abatacept, demonstrating the effect of this drug on the immune microenvironment. The results demonstrate that abatacept is a promising therapeutic strategy for the treatment of cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01954979. (© 2023 by The American Society of Hematology.)
Databáze:	MEDLINE
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