Dr Alderuccio on Loncastuximab Tesirine With Rituximab in R/R Follicular Lymphoma

“We observed that [51% of patients had progression of disease within 24 months and 92%] presented with a high disease burden [based on GELF criteria]. The primary study end point was the [complete response] rate, and [per Lugano criteria, at week 12], we observed [an] overall response rate of [97%] with a CR rate of [67%]. [Based on these findings, the study met its primary end point]."

Juan Pablo Alderuccio, MD, associate professor of medicine, clinical site disease group leader in the Lymphoma Section, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses findings from a phase 2, single-center, single-arm study (NCT04998669) evaluating the combination of loncastuximab tesirine-lpyl (Zynlonta) with rituximab (Rituxan) in patients with relapsed or refractory follicular lymphoma (FL) who had received at least one prior line of systemic therapy.

This study enrolled 39 patients who presented with disease progression or relapse within 24 months (POD24) after first-line treatment, one or more Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria, or second relapse, and an ECOG performance status of 0 to 2.

Among these patients, 51% had POD24 and 92% had a high disease burden with at least 1 GELF criteria. The primary end point was the complete response (CR) rate at week 12, which was achieved in 67% of patients. The 12-week overall response rate was 97%.

At the current follow-up, CRs appeared durable, with a 12-month progression-free survival (PFS) rate of 94.6% (95% CI, 79.9%-98.6%). The median PFS has not been reached. The safety profile was consistent with prior studies in large B-cell lymphoma, with no new safety concerns. The most frequently reported adverse effects were grade 1 or 2, including hyperglycemia, elevated liver enzymes, fatigue, and rash.

These findings suggest that a fixed-duration regimen of loncastuximab tesirine with rituximab is an effective second-line and later treatment option for patients with FL. Given the high CR rates, durability of responses, and manageable safety profile, further validation in larger, multicenter studies is warranted to refine patient selection and establish the role of this combination in clinical practice.