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# FDA Questions Zynlonta’s Benefit/Risk: Report
- URL: https://www.fdaweb.com/fda-questions-zynlontas-benefit-risk-report/
- Published: 2026-08-13T12:00:00.000Z
- Updated: 2026-09-14T13:45:05.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5161620

ADC Therapeutics says that at a recent meeting with FDA, agency officials indicated that they have “substantial concerns regarding the benefit/risk or verification of clinical benefit” in the LOTIS-5 trial of the company’s Zynlonta (loncastuximab tesirine) to treat diffuse large B-cell lymphoma (DLBCL). In an online [report](https://pharmaphorum.com/news/fda-cites-significant-concerns-adc-lymphoma-trial?ref=fdaweb.com), *Pharmaphorum* says company officials said they were “assessing the best regulatory path forward” for Zynlonta and the LOTIS-5 data as a result of the meeting.

The newsletter reports that ADC also is investigating a combination of Zynlonta and Roche’s Columvi (glofitamab) as a second-line or later regimen in DLBCL.

*Pharmaphorum* says questions were raised in June when a company update showed that 13.2% of patients treated with Zynlonta in LOTIS-5 died, compared to 4.6% of the control arm. The company told investors that FDA was concerned about the imbalance in Grade 5 events, when assessed in the context of a marginal treatment benefit.

The report says Zynlonta was granted accelerated approval by FDA as a third-line or later treatment for DLBCL. The company intended LOTIS-5 to convert the accelerated approval to a full approval and move the drug into a second-line setting.

While Zynlonta and rituximab (Genentech/Biogen’s Rituxan) improved progression-free survival by 27% compared to Rituxan plus chemotherapy, *Pharmaphorum* says, there was no benefit on overall survival. “Add in the imbalance in deaths between the groups, and ADC’s plans for the drug seem speculative at best,” it says.