Loncastuximab Combination Shows Dramatic Activity in High-Risk, R/R Follicular Lymphoma

In patients with high-risk, relapsed or refractory follicular lymphoma (FL), loncastuximab combined with rituximab displayed robust efficacy, revealing its potential as a new treatment option for the patient population.¹

Findings come from a single-institution, phase 2, investigator-initiated study (NCT04998669), which aims to add to the scarcity of data around the activity of loncastuximab in FL and confirm the possible synergy between loncastuximab and rituximab.

Of the 39 patients enrolled, 35 were evaluable for efficacy and safety. The objective response rate (ORR) at week 12 was 97.1%, with a CMR rate of 68.6%. A partial metabolic response (PMR) rate of 28.6% was also observed at week 12. Each patient who achieved a CMR maintained response. As of the data cutoff date, data from one patient with a PMR has not been assessed. However, the response of four of 10 patients improved to CMR at week 21, showing a best CMR rate of 80%.

Among the 10 patients with FL bone marrow involvement at baseline, it was resolved at the week 12 reassessment. Moreover, an OR of 100% and CMR of 80% was seen in the POD24 group.

At a median follow-up of 15.6 months (range, 0.1-28.5 months), patients had a 12-month progression-free survival (PFS) rate of 94.2% (95% CI, 78.7-98.5%) and OS rate of 93.3% (95%CI, 75.6-98.3%). At the 18-month mark, the PFS rate was 90.1% (95% CI, 71.9-96.8%), and the OS rate was 93.3% (75.6-98.3%). The median PFS was not reached. Only two patients had disease progression to diffuse large B-cell lymphoma (DLBCL) and relapsed FL with asymptomatic and localized disease. The patient with DLBCL died during the study, and the other patients are on observation as of the data cutoff.

Regarding safety, the most common treated-emergent adverse events (AEs) were neutropenia (53.8%), alkaline phosphatase elevation (53.8%), anemia (46.1%), maculopapular rash (46.1%), fatigue (43.5%), and aspartate aminotransferase and alanine aminotransferase elevation (38.4% each, respectively). The only AE that was grade 3 or higher was neutropenia, and there was one case each of grade 2 urinary tract infection and fluid accumulation. There were no treatment-related deaths during the study.

The study included adult patients with high-risk, relapsed or refractory FL treated with one or more prior line of systemic therapy who presented with POD24 or GELF criteria. Patients received four weekly doses of intravenous (IV) rituximab 375 mg/m² followed by one dose every eight weeks for a total of five doses in combination with loncastuximab IV 0.15 mg/kg every three weeks for two doses followed by 0.075 mg/kg every three weeks for a total of seven doses.

The combination therapy initially lasted for 21 weeks, but patients who achieved a complete metabolic response (CMR) discontinued loncastuximab and continued treatment with two additional doses of rituximab, every eight weeks. Patients in the study were premedicated with dexamethasone 4 mg twice daily for three days. Prophalyaxis was not included in the study protocol.

Investigators deemed the activity of the loncastuximab, and rituximab to be dramatic with robust CMR and 12-month PFS rates. This data adds to phase 1 findings of single-agent loncastuximab in 14 patients with FL² and supports loncastuximab plus rituximab as a new therapeutic option for high-risk, relapsed or refractory FL.¹

REFERENCE

1. Alderuccio JP. Alencar AJ, Schatz JH, et al. Loncastuximab tesirine with rituximab induces robust and durable complete metabolic responses in high-risk relapsed/refractory follicular lymphoma. Presented at: 66^th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA. Abstract 337.
2. Hamandani M, Radford J, Carlo-Stella C, et al. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2921;137(19):2634-2645. doi: 10.1182/blood.2020007512