Phase 2 Study of Acalabrutinib Window Prior to Frontline Therapy in Untreated Aggressive B-Cell Lymphoma: Preliminary Results and Correlatives of Response to Acalabrutinib

Background: Diffuse large B-cell lymphoma (DLBCL) subtypes have differential response to BTK inhibitors (BTKi). Ibrutinib with R-CHOP improves survival in DLBCL subsets, but toxicity is limiting. Precise characterization of BTKi-responsive tumors enhances pt selection. Acalabrutinib (acala) is a BTKi with activity in DLBCL, but the molecular correlates of acala response are unknown. Circulating tumor DNA (ctDNA) is a prognostic biomarker in DLBCL including early changes during chemotherapy. PhasED-Seq is a novel ctDNA method that lowers the error profile of mutation detection by requiring the concordant detection of two separate mutations on an individual cell-free DNA molecule (Kurtz et al. Nat Biotechnol 2021). We employed a response-adapted study of acala for up to 14d prior to frontline therapy for aggressive B-cell lymphoma to determine the molecular profile of BTKi-responsive tumors. We report preliminary results including dynamic changes in ctDNA from this ongoing trial [NCT04002947].