Exceptional Responder Leads to a Clinical Trial
One such patient is a 26-year-old woman with Hodgkin's lymphoma who presented after relapsing following nine standard lines of therapy, including an allogeneic stem cell transplant. She was initiated on a mTOR and a histone deacetylase inhibitor therapy, leading to a near-complete response and enabling her to receive a second transplant. Immunocorrelative and proteomic analysis revealed new insights into the biology of Hodgkin's lymphoma in terms of the response signature that centered on an immune dysregulation involving an imbalance between effector and functional Tregs, in addition to targeting the mTOR pathway. This case study highlights the need for an approach that focuses on combinatorial therapies that target both the pathogenesis and adaptive responses to envisioned therapies. Based on this single patient response, a Phase I clinical trial with combinatorial vorinostat and sirolimus was amended to include Hodgkin's lymphoma patients, and the preliminary results demonstrate a breakthrough for advanced Hodgkin's lymphoma.