ADC Therapeutics’ confirmatory Phase 3 LOTIS-5 dataset for Zynlonta (polatuzumab vedotin?—as described in the provided text: Zynlonta plus rituximab) has raised serious safety concerns and undermined efficacy in diffuse large B-cell lymphoma. The company reported 27 deaths in the Zynlonta arm versus nine in the control arm, with analysts flagging that the elevated death rate could complicate second-line utilization. Beyond mortality, the company also reported no overall survival benefit in patients treated with the Zynlonta-based regimen. ADC had previously secured FDA accelerated approval in April 2021 for relapsed or refractory DLBCL in later settings, and LOTIS-5 was intended to support broader approval. The immediate market impact has been sharp—ADC shares reportedly fell more than 50%—and the confirmatory readout adds uncertainty around how the program could proceed with regulatory review.