According to a July 11 article from Maaisha Osman, commercial-stage biotechnology company ADC Therapeutics has voluntarily halted enrollment for the Phase 2 LOTIS-9 study evaluating Zynlonta (loncastuximab tesirine-lpyl) and rituximab. The study sought to understand the safety and efficacy of this treatment combination in people with treatment-naive (untreated) diffuse large B-cell lymphoma (DLBCL). Zynlonta has previously been approved under Accelerated Approval for people with DLBCL who relapsed or whose condition remained refractory after two or more lines of systemic therapy.

The announcement that no new patients would be enrolled came after seven participants within the trial died. Altogether, 40 participants enrolled initially. 12 participants experienced adverse respiratory effects. Of these, five were grade 3-4 respiratory-related treatment-emergent adverse events and seven were Grade 5 fatal events. 100% of the people who died had underlying cardiac and respiratory comorbidities and were 80+ years old.

In a separate news release from ADC Therapeutics, the company shared:

As per investigator assessment, eleven of the twelve counts were individually assessed as unlikely or unrelated to study drug [and] four out of the five Grade 3 or Grade 4 events have since resolved. The cause of these events remains under further investigation.

Some researchers question whether Zynlonta would be safe on its own or in a lower dose, and that the safety issues could be caused by the combination treatment. The company and regulatory officials are now looking into these deaths. ADC Therapeutics chose to pause enrollment while the investigation occurs to protect and preserve patient health and safety. Additional information should be available by the end of 2023 or early 2024.

About Diffuse Large B-Cell Lymphoma (DLBCL)

Diffuse large B-cell lymphoma is an aggressive, fast-growing cancer. It exists under the greater umbrella of non-Hodgkin’s lymphoma; in fact, it is the most common form of NHL. Doctors don’t know exactly what causes DLBCL. However, there are risk factors. If you have an autoimmune disease, a family history of DLBCL, or are immunocompromised, your risk increases. DLBCL causes the body to create abnormal B-lymphocytes. Normally, these lymphocytes help your body fight infection. But when the lymphocytes are abnormal, they spread out throughout your body and cause health issues.

Because DLBCL is so aggressive, it is important to begin treatment as soon as possible after diagnosis. If you have recently been diagnosed, please speak with your care team to determine the best course of action. Treatment options include chemotherapy, radiation, bone marrow transplants, immunotherapy, and surgery. Symptoms of this cancer may include:

• Painless but swollen lymph nodes
• Itchy skin
• Unintended wight loss (more than 10% of your body weight over 6~ months)
• Fever and drenching night sweats
• Abdominal pain or pressure
• Shortness of breath