ADC Therapeutics disclosed top-line confirmatory Phase 3 data for Zynlonta (loncastuximab tesirine) plus rituximab in relapsed or refractory DLBCL, with increased death counts in the treatment arm complicating the push toward full approval. The report said the overall survival benefit was not demonstrated and 27 deaths occurred in the Zynlonta arm versus nine in control. In parallel, Fulcrum Therapeutics disclosed a restructure after FDA concerns in sickle cell disease led it to discontinue its lead PRC2-targeting program pociredir. The company said the regulator determined that PRC2-targeting interventions carry equivalent malignancy risk, prompting the biotech to exit development and seek strategic alternatives. Together, the disclosures underline how safety signals and regulatory benefit–risk evaluations can rapidly reshape timelines, force portfolio cuts and alter shareholder expectations in late-stage oncology and hematology.