PF513 mutations affecting the CREBBP hat domain predict response to MTOR inhibitors Everolimus and Temsirolimus in relapsed/refractory follicular lymphoma | Kumar E, et al | HemaSphere | Jun. 2019

Abstract

With an expanding array of novel treatment options in follicular lymphoma (FL), we largely lack effective biomarkers to predict response in this molecularly heterogeneous disease. Activating mutations focused on components of the nutrient-sensing arm of the mTORC1 pathway (RRAGC, ATP6V1B2, ATP6AP1), are particularly enriched in FL, occurring in ∼30% of cases. Meanwhile, clinical mTOR inhibitors (mTORi) have shown some promise, with response rates of 50–60% in relapsed/refractory FL. We therefore sought to determine whether gene mutation status - particularly in genes regulating the mTOR pathway – may represent biomarkers of mTORi-response in FL.