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Differential gene expression profile correlates with bortezomib responsiveness in steroid-resistant cGVHD

ABSTRACT: Nineteen patients with steroid-refractory cGVHD (chronic graft versus host disease) received weekly bortezomib from 2 – 12 months (1.6 mg/m2 q wk x 4 followed by one week of rest). Treatment was well tolerated with no > grade 3 adverse events. Six patients achieved CR or good PR (gPR). Average Rodnan scores decreased from 22.6 ± 12.8 to 5.9 ± 6.2 (p<0.005) for 8 patients with sclerosis who completed > 2 treatments, including one patient with marked healing of suppurating lesions and significantly reduced chronic diarrhea in another. Thus, weekly bortezomib was safe and produced early improvements in some patients with longstanding refractory disease. CR or gPR correlated with a younger age and lower number of involved organs with a severity score of > 2. Based on gene expression array and pathway analyses, High Responders displayed an immune response profile that resembled that of hematopoietic stem cell-transplanted patients without cGVHD. By comparison, Low Responders showed markedly altered gene expressions in both cell-mediated immune response and proinflammatory pathways. Our preliminary findings suggest that bortezomib responsiveness may be predicated by distinct immunopathological manifestations among cGVHD patients. This trial was registered at www.clinicaltrials.gov as NCT01158105.

ORGANISM(S): Homo sapiens

PROVIDER: GSE56495 | GEO | 2017/01/18

SECONDARY ACCESSION(S): PRJNA243507

REPOSITORIES: GEO

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