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Everolimus is a small molecule oral inhibitor of the mammalian target of rapamycin (mTOR), specifically targeting the mTORC1 pathway. In the context of clinical research led by the University of Cologne and the German Hodgkin Study Group (GHSG), everolimus was evaluated in combination with the DHAP reinduction chemotherapy regimen (comprising dexamethasone, high-dose cytarabine, and cisplatin). This combination was investigated in a Phase I/II clinical trial (GHSG HD-R3i, NCT01453504) for patients with relapsed or refractory classical Hodgkin lymphoma who were eligible for autologous stem cell transplantation. The rationale for the combination is based on the frequent activation of the mTORC1 pathway in Hodgkin lymphoma tumor samples. While the combination was found to be feasible and safe, the trial did not meet its primary efficacy endpoint of achieving a 40% or greater complete remission rate.
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