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Summary: Despite the clinical and molecular heterogeneity of follicular lymphoma (FL), there remains a lack of biomarker‐directed therapeutic approaches in routine clinical practice, with the notable exception of the EZH2 inhibitor tazemetostat in EZH2‐mutant FL. Here we examined whether gene mutation status predicts response to clinical mTOR inhibitors (mTORi) in FL, by performing targeted mutational profiling of biopsies from 21 relapsed/refractory FL patients treated with mTORi everolimus or temsirolimus within clinical trials. We observed an enrichment of mutations within the catalytic histone acetyltransferase (HAT) domain of CREBBP in mTORi‐responders, and describe distinct transcriptional characteristics and co‐occurring mutations of FL harbouring these mutations; reinforcing the growing appreciation of CREBBPHAT mutation as a key biological determinant and its promise as a therapeutic biomarker in FL. [ABSTRACT FROM AUTHOR]

Relapsed or refractory non-Hodgkin B-cell lymphoma is an aggressive disease with a dismal prognosis. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a viable treatment option with durable remissions observed in clinical trials. Due to the risk of toxicities such as cytokine release syndrome and neurotoxicity, careful patient selection is critical to optimize outcomes. Narrow selection criteria were used in clinical trials that led to approval, but a wider range of patients has been successfully treated in the commercial setting. Due to lack of validated pretreatment clinical factors, including risk scores or biomarkers to predict efficacy and toxicity, choosing candidates for CAR T-cell therapy currently relies on expert opinion. Because of logistical constraints and often aggressive disease, we favor referring patients early for cellular therapy at the time of first treatment failure. Herein, we discuss criteria for patient selection using a case-based approach informed by reports of real-world outcomes. [ABSTRACT FROM AUTHOR]