Loncastuximab Tesirine Shows Promise Treating Diffuse Large B-cell Lymphoma

A phase 2 clinical trial of loncastuximab tesirine conducted at the MUSC Hollings Cancer Center showed promise as a new treatment for aggressive B-cell lymphoma, according to results published in Lancet Oncology.

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of aggressive B-cell non-Hodgkin lymphoma (NHL), begins in the lymph nodes, spleen or bone marrow. Because two-thirds of patients have a durable response to frontline therapy, the remaining one-third of patients relapse or are refractory to frontline treatment and typically have a poor prognosis.

The open label trial was available to patients 18 years of age and older with relapsed or refractory DLBCL after 2 or more lines of treatment. According to researcher and lymphoma specialist Brian Hess, MD, this trial was significant because it included a difficult-to-treat patient population.

"Traditional chemotherapy is very unlikely to lead to a sustained response in this patient population,” Hess said in the press release. “CD19 [chimeric antigen receptor (CAR)] T-cell therapy is now approved and provides hope for durable response and cure for the majority of these patients; however, not everyone is a candidate for CAR T-cell therapy. In addition, the majority of patients that receive CD19 CAR T-cell therapy eventually relapse and are in need of novel therapies such as loncastuximab.”

The LOTIS-2 trial tested the efficacy of loncastuximab tesirine, which is an antibody-drug complex that targets CD19. The drug works by attaching to CD19, which delivers its payload into the cell and minimizing systemic toxicity. Once internalized, the drug damages the DNA of the lymphoma cells, leading to cell death, according to the study.

"This is a novel mechanism of action that provides potential benefit for patients who otherwise do not have a lot of options," Hess said in the release. "For patients who are not candidates for, not interested in, or relapse after CAR T, this could be a promising therapy option. Additionally, the drug is delivered intravenously every 3 weeks, so patient proximity to treatment centers is less critical for this therapy."

In the trial, the overall response rate was 48%, with approximately 50% of patients with relapsed DLBCL who had already tried 2 or more treatments showing a complete or partial response to the therapy.

The next step after the approval of loncastuximab tesirine as a single agent is to combine it with other agents to see if this improves efficacy and durability of response in the upcoming months, according to the study authors.

"I am excited that this therapy can now be given to patients who may live 2 to 3 hours away from Charleston, South Carolina, and not want or be able to travel to MUSC for treatment,” Hess said in the press release. “We look forward to providing education on the potential efficacy and toxicity of this agent to oncology practitioners throughout the state of South Carolina so that patients can receive this therapy locally.”

REFERENCE

Phase two CD19-antibody-drug conjugate trial demonstrates promise for aggressive lymphoma. EurekAlert! July 23, 2021. Accessed July 26, 2021. https://new.eurekalert.org/pub_releases/2021-07/muos-ptc072321.php