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Published on: January 2, 2017
Therapy of sclerodermatous chronic graft-versus-host disease with mammalian target of rapamycin inhibitors
Zuzana Jedlickova1, Irina Burlakova, Gesine Bug
1Centre for Bone Marrow and Blood Stem Cell Transplantation, Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
Abstract:
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.
Insights
Mammalian target of rapamycin inhibitors (mTOR-I) show promise for treating severe sclerodermatous chronic graft-versus-host disease (cGVHD). This study found a 76% response rate, enabling steroid reduction in many patients.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Sclerodermatous chronic graft-versus-host disease (cGVHD) is a debilitating complication post-hematopoietic stem cell transplantation.
- Limited effective treatment options exist for severe sclerodermatous cGVHD.
- Mammalian target of rapamycin inhibitors (mTOR-I) have emerged as a potential therapeutic strategy.
Purpose of the Study:
- To evaluate the efficacy and safety of mTOR-I in patients with severe sclerodermatous cGVHD.
- To assess the response rates, survival, and adverse events associated with mTOR-I therapy.
- To determine if mTOR-I can facilitate the reduction of concomitant immunosuppressive medications.
Main Methods:
- Retrospective analysis of 34 patients with severe sclerodermatous cGVHD treated with mTOR-I.
- Patients received either mTOR-I monotherapy or combination therapy, with doses adjusted to low therapeutic levels (3-8 ng/mL).
- Data on treatment response, adverse events, medication tapering, and survival were collected and analyzed.
Main Results:
- An overall response rate of 76% was observed (6 complete responses, 20 partial responses).
- Concomitant medications, including steroids, were tapered and discontinued in a significant number of patients.
- Major adverse events included hyperlipidemia and impaired wound healing; overall 3-year survival was 72%.
Conclusions:
- mTOR-I represent a potentially effective and well-tolerated treatment for severe sclerodermatous cGVHD.
- The observed response rates and ability to reduce steroid burden support the use of mTOR-I in this patient population.
- Further prospective studies are warranted to confirm these findings and optimize treatment strategies.
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