Therapy of Sclerodermatous Chronic Graft-Versus-Host Disease with Mammalian Target of Rapamycin Inhibitors

• Published in: Biology of blood and marrow transplantation 2011-05, Vol.17 (5), p.657-663
• Main Authors: Jedlickova, Zuzana, Burlakova, Irina, Bug, Gesine, Baurmann, Herrad, Schwerdtfeger, Rainer, Schleuning, Michael
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Combined Modality Therapy - methods; Everolimus; Female; Graft vs Host Disease - mortality; Graft vs Host Disease - pathology; Graft vs Host Disease - therapy; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - therapeutic use; Male; Middle Aged; Photopheresis; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Recurrence; Retrospective Studies; Scleroderma, Systemic - mortality; Scleroderma, Systemic - pathology; Scleroderma, Systemic - therapy; Sclerodermatous chronic GVHD; Sirolimus; Sirolimus - administration & dosage; Sirolimus - adverse effects; Sirolimus - analogs & derivatives; Sirolimus - therapeutic use; Steroids - administration & dosage; Steroids - therapeutic use; Survival Analysis; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism; Transplantation, Homologous; Treatment Outcome; Young Adult
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2010.07.025

This retrospective study analyzes 34 patients with severe sclerodermatous chronic graft-versus-host disease (cGVHD) treated with inhibitors of the mammalian target of rapamycin (mTOR-I). Twelve patients received mTOR-I as monotherapy and 22 a combination therapy. Four patients also received extracorporal photopheresis. mTOR-I were applied as first-line therapy (n = 15) or in refractory disease (n = 19). Drug doses were adjusted to low therapeutical levels (3-8 ng/mL). Six and 20 patients had a complete and a partial response, respectively, with an overall response rate of 76%. Two additional patients had stable disease. Six refractory patients required alternative therapy. Comedication, especially steroids, could be tapered and stopped in a significant number of patients. No difference in response was observed in everolimus- and sirolimus-treated patients. Major adverse events possibly related to mTOR-I were hyperlipidemia and impaired wound healing. Two patients developed thrombotic microangiopathy. Eight patients died, 5 of the nonresponders (cGVHD; n = 3, infection; n = 2) and 3 of the responders (relapse of the underlying malignancy; n = 1, secondary malignancy; n = 1, unknown cause; n = 1). Twenty-six of the 34 patients remain alive, 18 still on therapy with mTOR-I. Median follow-up for surviving patients is 723 days (range 88-1621). The overall survival at 3 years since mTOR-I is 72%. In conclusion, mTOR-I seem to be an effective and well-tolerated treatment option for patients with sclerodermatous cGVHD.