ASH 2024: High Response Rates Observed with Loncastuximab Tesirine Plus Rituximab in High-Risk Patients with Relapsed/Refractory FL

Loncastuximab tesirine (loncastuximab) is an antibody-drug conjugate used to treat certain types of B-cell lymphomas. The phase I study of loncastuximab showed promise in a small group of patients with relapsed/refractory follicular lymphoma (FL) as well, but further studies in this population have been lacking. Investigators therefore led a phase II study to evaluate the efficacy and safety of loncastuximab in combination with rituximab
for patients with relapsed/refractory FL. Results from this study were presented by Foundation grantee Juan Alderuccio, MD of Sylvester Comprehensive Cancer Center.

The study included 39 adults from a single institution who had previously received at least 1 line of systemic therapy for FL (range, 1 to 6). Patients ranged in age from 47 to 89 years and consisted primarily of those with advanced (82%) and high-risk disease (61.5%). Most patients (56.5%) received first-line R-CHOP.

Among 35 patients with available response data, the overall response rate at 12 weeks was 97.1%. A complete metabolic response, as observed using PET/CT scan, was observed in 68.6% of participants, and a partial metabolic response was observed in 28.6%. All complete metabolic responses were maintained, and 40% of the partial metabolic responses observed improved to a complete response at week 21. The 12-month progression-free survival rate was 94.2% and the overall survival rate was 93.3%. The overall survival rate was maintained up to 18 months, and more than 90% of patients remained progression-free at 18 months.

The most common adverse events included neutropenia, elevations in liver enzymes, anemia, maulopapular rash, and fatigue. Fluid accumulation was also reported but was mostly mild and was treatable with diuretics. Five cases of severe neutropenia were eported. No treatment-related deaths occurred during the trial.

The authors concluded that the results of the study demonstrate “dramatic” activity for loncastuximab plus rituximab in patients with high-risk relapsed/refractory lymphoma, and note that a multicenter expansion study is currently in progress.

This study also included contributions from former Foundation SAB member Izidore Lossos, MD of Sylvester Comprehensive Cancer Center, and Craig H. Moskowitz, MD of Sylvester Comprehensive Cancer Center; and Foundation former grantee Jonathan H. Schatz, MD of University of Miami.