An 80-year-old woman with relapsed nodal T-follicular helper cell lymphoma, not otherwise specified, developed severe watery diarrhea during valemetostat therapy...To the best of our knowledge, this is the first reported case of enhancer of zeste homolog 1 and 2 (EZH1/2) inhibitor-induced colitis. EZH1/2 inhibition may lead to T cell-mediated intestinal injury through epigenetic dysregulation; therefore, patients receiving EZH1/2 inhibitors who develop persistent diarrhea should undergo early endoscopic and histological evaluations.

P1, N=4, Not yet recruiting, Daiichi Sankyo Inc.

At the last follow-up, four patients were alive without disease, four were alive with disease, and three died due to progressive disease. Hence, valemetostat is a promising salvage therapy for relapsed adult T-cell leukemia/lymphoma after allo-HCT.

P2, N=900, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting

P1/2, N=76, Recruiting, Novartis Pharma AG | Not yet recruiting --> Recruiting

P1/2, N=21, Completed, Daiichi Sankyo Inc.

P1/2, N=76, Not yet recruiting, Novartis Pharma AG

P1/2, N=600, Not yet recruiting, Institut Gustave Roussy

P1/2, N=54, Recruiting, Novartis Pharma AG

P1/2, N=203, Recruiting, Dizal Pharmaceuticals | Not yet recruiting --> Recruiting

P1, N=24, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | N=36 --> 24 | Trial completion date: Jan 2030 --> Jan 2029 | Trial primary completion date: Feb 2028 --> Feb 2027

Employing Micro-C, a micrococcal nuclease-based 3D genome mapping technique, we show that EZH1/2 inhibition with Valemetostat induced significant changes at multiple genome organizational levels (compartment, topological associated domain, and chromatin loop) without incurring cell death in NE SCLC...Notably, EZH1/2 inhibition reactivated Class I MHC expression by facilitating enhancer-promoter looping. Our results demonstrate that repression of a subset of EZH2 targets including Class I MHC genes is affected through modulation of 3D genome structure to the level of chromatin looping and further support clinical investigation of EZH2 inhibition in boosting therapeutic efficacy of ICI in SCLC patients.