The Effect of mTORC1 Inhibitor Everolimus in Patients with Relapsed T-Cell Lymphoma
Everolimus is an oral agent that targets the mTOR pathway. Mayo Clinic researchers, first author Mamta Gupta, conducted a study published in the journal Blood to investigate mTOR pathway activation in T cell lymphoma (TCL) cell lines and assess anti-tumor activity in patients with relapsed/refractory TCL in a Phase II trial.
The mTOR pathway was activated in all six TCL cell lines tested and everolimus strongly inhibited malignant T cell proliferation with minimal cytotoxic effects. Everolimus completely inhibited phosphorylation of ribosomal S6, a raptor/mTORC1 target, without a compensatory activation of the rictor/mTORC2 target Akt (S475).
In the clinical trial, 16 patients with relapsed TCL were enrolled and received everolimus 10 mg PO daily. Seven patients had cutaneous (all mycosis fungoides); four peripheral T-cell NOS; two anaplastic large cell; and one each of extranodal NK/T-cell, angioimmunoblastic, and precursor T lymphoblastic leukemia/lymphoma types.
The overall response rate was 44 percent. The median PFS was 4.1 months and the median OS 10.2 months. The median duration of response for the seven responders was 8.5 months.
These results indicate that everolimus has anti-tumor activity and provide proof-of-concept that targeting the mTORC1 pathway in TCL is clinically relevant.