The Oral Mtor Inhibitor Everolimus in Relapsed and Refractory Hodgkin Lymphoma- Compassionate Use in 8 Centers in Brazil

Purpose- Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin Lymphoma (HL). The goal of this study was to evaluate the response, time of response, toxicity and overall survival in patients with refractory disease using everolimus out of clinical trial, in a compassionate use.

Patients and Methods- Patients were eligible if they had refractory and active Hodgkin disease. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Time to response assessement was defined by each center until progression (this was defined by each doctor, some have considered to keep the drug until clinical progression and not radiological progression of the disease). Patients could remain on drug until progression or toxicity.

Results- Thirty three patients were enrolled. Median age at the time of everolimus start was 29 years (range, 20-70). Patients had received a median of 5 prior therapies (range, 3-7) , 81% had undergone prior autologous stem cell transplant and 4 patients had undergone alogenic trasnplantation. The ORR was 51% (95% CI: 24-71%) with 14 patients achieving a PR, 3 patient achieving a CR and 10 with stable disease. Thirteen patients used the drug for more than 1 year. Patients received a median of 14 cycles of therapy and 3 remains on therappy at 36 months showing a great tolerability of the drug. The median DR for the responders (CR/PR) was 10 months. The most commons site effects were trombocitopenia and hypercholesterolemia. Three patients had pulmonar toxicity. The adverse events grade III and IV ocurred in 30% of the patients.

Conclusions- Everolimus has single-agent activity in relapsed/refractory HL, even in real lyfe and clinical practice and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant.