Dr Alderuccio on Loncastuximab Tesirine Plus Rituximab in High-Risk R/R Follicular Lymphoma

"The primary study end point was the complete response [CR] rate at week 12 by Lugano criteria, and we observed [a 12-week] overall response rate of 97.4% with a CR rate of 66.7%. Based on this result, the study met its [primary end point].

Juan P. Alderuccio, MD, an assistant professor of clinical medicine at Sylvester Comprehensive Cancer Center, University of Miami Health System, discussed results from a phase 2, investigator-initiated, single-arm study (NCT04998669) evaluating the efficacy and safety of loncastuximab tesirine (Zynlota) in combination with rituximab (Rituxan) in patients with high-risk, relapsed/refractory follicular lymphoma.

The study’s primary end point was complete response (CR) rate at week 12 per Lugano criteria. At 12 weeks, the overall response rate (ORR) was 97.4%, and the CR rate was 66.7%. The best ORR and best CR rate at any point were 97.4% and 76.9%, respectively. The 12-month progression-free survival (PFS) rate was 94.6%, and the median PFS was not yet reached.

The safety profile of the regimen was consistent with prior studies of loncastuximab tesirine in large B-cell lymphoma, and no new safety signals were observed. Most adverse effects were grade 1 or 2, and the most common included hyperglycemia, elevated liver enzyme levels, fatigue, and rash. No unexpected toxicities were reported, and the combination was generally well tolerated.

This study highlighted the potential role of a fixed-duration regimen of loncastuximab tesirine plus rituximab as an effective therapeutic strategy in second-line and later settings for patients with follicular lymphoma, particularly those with high tumor burden and early relapse following first-line therapy, Alderuccio explained. The depth and speed of response, along with the manageable safety profile, underscored the rationale for further investigation of this antibody-drug conjugate–based regimen in broader clinical trials.