304 (PB084) - Pharmacological screening identified promising combination partners in marginal zone lymphoma models with secondary resistance to BTK and PI3K inhibitors

Abstract

Background. Marginal zone lymphoma (MZL) is an indolent yet incurable B-cell malignancy. Two BTK inhibitors, ibrutinib and zanubrutinib, are FDA approved for relapsed/refractory MZL patients. PI3K inhibitors have also shown clinical activity although their use has been recently reduced due to toxicities. We have previously reported a model of resistance to BTK/PI3K inhibitors developed by prolonged exposure to the PI3K-delta inhibitor idelalisib (Arribas, ASH2019). Here, we present the data from a large pharmacological screen with over 1,500 compounds in this MZL model.