A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA antibodies.

Publication Type:

Journal Article


Blood, Volume 118, Issue 15, p.4070-4078 (2011)


2011, Adrenal Cortex Hormones, Adult, Aged, Antibodies, Monoclonal, Center-Authored Paper, Clinical Research Division, Disease-Free Survival, Drug Resistance, Female, Follow-Up Studies, Graft vs Host Disease, Humans, Male, Middle Aged, Piperazines, Pyrimidines, Receptor, Platelet-Derived Growth Factor alpha, September 2011


Stimulatory anti-platelet derived growth factor receptor alpha (PDGFRA) antibodies have been associated with extensive chronic graft-versus-host disease (cGvHD). We performed a phase 1 dose escalation trial of imatinib in corticosteroid dependent / refractory cGvHD to assess the safety of imatinib and test the hypothesis that abrogation of PDGFRA signaling can ameliorate the manifestations of cGvHD. Fifteen patients were enrolled. Mean follow-up time was 56.6 (18-82.4) weeks. Imatinib 400 mg daily was associated with more frequent moderate to life threatening adverse events than 200 mg daily. The main adverse events were nausea, edema, confusion, diarrhea, liver function test elevation, fatigue, and myalgia. The overall response rate was 40% (6/15). The treatment failure rate was 40% (6/15). 20% (3/15) of subjects had stable disease. Of four subjects with phospho-PDGFRA and phospho-PDGFRB immunohistochemistry studies before and after treatment, inhibition of phosphorylation was observed in three but correlated with response in one. Anti-PDGFRA antibodies were observed in 7/11 evaluable subjects but correlated with clinical activity in four. We conclude that cGvHD responds to imatinib through multiple pathways that may include PDGFRA signal transduction. This study is registered at ClinicalTrials.gov (NCT00760981).