A recent clinical trial for Zynlonta, a medication used to treat a type of blood cancer called diffuse large B-cell lymphoma (DLBCL), has raised important safety concerns. The trial, called LOTIS-5, included 440 patients whose cancer had either returned or did not respond to previous treatments. In the study, patients received either Zynlonta combined with another drug, Rituxan, or Rituxan combined with two chemotherapy drugs, gemcitabine and oxaliplatin. The results showed that 13.2% of patients in the Zynlonta group (27 people) died during the study, compared to 4.6% in the control group (9 people). Most of these deaths occurred in patients aged 75 and older and were due to infections. The company noted that the higher number of deaths might also be because patients in the Zynlonta group were monitored more closely than those in the control group. The study also found a higher rate of serious side effects in the Zynlonta group (49%) compared to the control group (34.5%), as well as more patients stopping treatment due to side effects (25.5% vs. 9.1%). Despite these concerns, the Zynlonta and Rituxan combination did show some positive effects, such as longer time without the cancer worsening (6.1 months vs. 4.7 months), a higher rate of complete cancer response (39.5% vs. 26.7%), and a longer duration of response (16.8 months vs. 12.3 months). Importantly, there was no negative impact on the overall survival of patients. The trial was designed to help get full approval for Zynlonta and allow it to be used earlier in treatment. However, the company’s stock price dropped sharply by 52% after the results were announced. Zynlonta is the only commercial product for ADC Therapeutics, with sales of $74 million last year and $20 million in the first three months of this year. The company has enough funds to continue operations until 2028. The company plans to meet with the FDA in August to discuss these results and submit for approval in late 2024. Additionally, Zynlonta is being studied in combination with another drug, Columvi, for treating another type of blood cancer, and early results from a small study showed only 2 deaths out of 49 patients.