Pharmacodynamic Monitoring Predicts Outcomes of CCR5 Blockade as Graft-versus-Host Disease Prophylaxis.
Biol Blood Marrow Transplant
; 24(3): 594-599, 2018 03.
Article
in En
| MEDLINE
| ID: mdl-29061535
ABSTRACT
Blocking lymphocyte trafficking after allogeneic hematopoietic stem cell transplantation is a promising strategy to prevent graft-versus-host disease (GVHD) while preserving the graft-versus-tumor response. Maraviroc, a CCR5 antagonist, has shown promise in clinical trials, presumably by disrupting the migration of effector cells to GVHD target organs. We describe a phosphoflow assay to quantify CCR5 blockade during treatment with maraviroc and used it to evaluate 28 patients in a phase II study. We found that insufficient blockade of CCR5 was associated with significantly worse overall survival (HR, 10.6; 95% CI, 2.2 to 52.0; P = .004) and higher rates of nonrelapse mortality (HR, 146; 95% CI, 1.0 to 20,600; P = .04) and severe acute GVHD (HR, 12; 95% CI, 1.9 to 76.6; P = .009). In addition, we found that pretransplant high surface expression of CCR5 on recipient T cells predicted higher nonrelapse mortality and worse GVHD- and relapse-free survival. Our results demonstrate that pharmacodynamic monitoring of CCR5 blockade unravels interpatient variability in the response to therapy and may serve as a clinically informative biomarker.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Receptors, CCR5
/
CCR5 Receptor Antagonists
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Maraviroc
/
Graft vs Host Disease
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Year:
2018
Type:
Article