Abstract
There is no standard-of-care for treatment of relapsed/ refractory (rel/ref) follicular lymphoma (FL). Loncastuximab tesirine (loncastuximab) is an antibody-drug conjugate directed against CD19. Here we report initial results of a single-institution study evaluating this combination in rel/ref FL (NCT04998669). Adult patients with rel/ref FL previously treated with ≥1 line of systemic therapy presenting GELF criteria or progression of disease within 24 months (POD24) at enrollment were eligible. Primary study endpoint was complete response (GR) by week 12 PET/GT. The initial 21 weeks of therapy consisted of 4 weekly doses of rituximab i.v. 375mg/m2 followed by 1 dose every 8 weeks for a total of 5 doses in association with loncastuximab i.v. 0.15mg/kg every 3 weeks for 2 doses followed by 0.075mg/kg every 3 weeks for a total of 7 doses. Premedication with dexamethasone 4 mg twice daily for 3 days was required. Patients achieving GR at week 21 discontinued loncastuximab and received two doses of rituximab every 8 weeks. Twenty-six patients have been enrolled from January 2022 to July 2023,25 evaluable for toxicity and 21 for response. Median age was 68 years (range 47 to 89). Most were women (n=14; 54%), with advanced-stage (11=20; 77%), high-risk FLIPI score (n=i3; 50%), and 12 (46%) demonstrating POD24 after immunochemotherapy. Median lines of prior therapy were 1 (range 1 to 6). Most common adverse events included alkaline-phosphatase, ALT, AST elevation; maculo-papular rash, fatigue, thrombocytopenia, photosensitivity, leg edema, anasarca and neutropenia. All toxicities resolved with supportive management and dose delays (n= 4). GR was observed in 7 of the initial 10 patients meeting pre-specified criteria to proceed to stage II. Among 21 patients evaluable for response, the overall response rate at week 12 was 95.2% [GR rate of 66.7% (n=i4), partial response (PR) rate of 28.6% (n=6)]. All GR were maintained and 4 of the 6 PR (2 patient have not yet re-evaluated) improved to GR at week 21 for a best GR rate of 86% (n= 18). All seven patients who completed the study remained in G R after end of treatment for a median follow up of 4.8 months (range 3.2 to 6.7). Loncastuximab with rituximab in patients with rel/ref FL is well tolerated and highly effective with a metabolic G R rate.