ADC Loncastuximab Tesirine Induces High Response Rates in Patients with High-Risk Follicular Lymphoma and Marginal Zone Lymphoma

Loncastuximab tesirine is a CD19-directed antibody and alkylating agent currently FDA-approved to treat refractory or relapsed large B-cell lymphoma in adults. The antibody-drug conjugate (ADC), marketed by ADC Therapeutics under the brand name Zynlonta, received accelerated approval in April 2021. Full approval is contingent upon positive results from confirmatory trials.

Meanwhile, ADC Therapeutics is working on expanding indications for the investigational ADC.

At the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition last month, the company announced positive results for loncastuximab tesirine phase 2 trials in the treatment of high-risk refractory or relapsed follicular lymphoma and relapsed or refractory marginal zone lymphoma.

The first trial was led by Juan Pablo Alderuccio, M.D., hematologist and lymphoma specialist at the Sylvester Comprehensive Cancer Center, University of Miami. Izidore S. Lossos, M.D., professor of medicine and chief of the lymphoma section of the division of hematology at the Sylvester Comprehensive Cancer Center, led the second trial.

The first trial enrolled 39 patients with relapsed or refractory follicular lymphoma. Most had a high-tumor burden or had disease progression within 24 months of starting treatment. The latter is typically referred to as POD24. Both are associated with worse prognosis. After receiving loncastuximab tesirine with rituximab (a CD20-directed antibody), study participants had an overall response rate of 97%, a complete response rate of 80%, and a 12-month progression-free survival rate of 94%. Results for patients with POD24 were similar, with an overall response rate of 100% and a complete response rate of 80%.

The second study is an ongoing multicenter trial in which 22 patients with refractory or relapsed marginal zone lymphoma received loncastuximab tesirine alone. Marginal zone lymphoma is a rare type of blood cancer, making up about 7% of non-Hodgkin lymphomas. Complete response to treatment is rarely achieved in cases of relapsed marginal zone lymphoma. As of July 1, 2024, results showed an overall response rate of 85% and a complete response rate of 75%. Patients with POD24 had a complete response rate of 77%.

The most common adverse events in the follicular lymphoma trial were neutropenia and elevated liver enzyme levels. For patients with marginal zone lymphoma, the most common adverse effects were photosensitivity and skin rash and elevated liver enzyme levels.

The authors concluded that loncastuximab tesirine demonstrated clinically significant outcomes in high-risk patients with follicular lymphoma and those with marginal zone lymphoma. The robust complete response rates support the use of this treatment for both indications, they emphasized. The researchers are conducting a multicenter expansion cohort study of loncastuximab tesirine with rituximab for follicular lymphoma, while the marginal zone lymphoma trial is ongoing.