# A Phase II Study of 177Lu–Lilotomab Satetraxetan, a CD37 Antibody–Radionuclide Conjugate, as Third- or Later-Line Treatment of Rituximab-Refractory Follicular B-Cell Lymphoma Patients

## TL;DR

A clinical trial tested a radioactive treatment for advanced follicular lymphoma patients who no longer respond to standard therapies, showing moderate effectiveness with manageable side effects.

## Contribution

The study evaluates the efficacy and safety of a single-dose CD37-targeted radioimmunoconjugate in rituximab-refractory follicular lymphoma patients.

## Key findings

- The 40/15 regimen showed higher response rates and longer response durations compared to the 100/20 regimen.
- The most common severe adverse events were hematologic, with neutropenia and thrombocytopenia being the most frequent.
- Betalutin demonstrated a mild toxicity profile and clinically relevant response rates in heavily pretreated patients.

## Abstract

Background: CD37, an antigen highly expressed in B-cell malignancies, served as the target in the LYMRIT-37-01 Part B (PARADIGME) and Part C studies employing a single intravenous injection of the radioimmunoconjugate 177Lu–lilotomab satetraxetan (Betalutin®). Methods: Patients with follicular lymphoma (FL), grades I–IIIa, who had received at least two previous lines of therapy and were refractory to at least one previous regimen with rituximab or an anti-CD20 agent, were included. They were randomized to receive either a 40 mg lilotomab pretreatment and an activity dosage of 15 MBq/kg Betalutin (“40/15” regimen) or 100 mg/m2 of lilotomab and 20 MBq/kg of Betalutin (“100/20” regimen). In total, 109 patients were enrolled and received Betalutin, 72 of whom received the 40/15 regimen and 28 received the 100/20 regimen. An additional heavily pretreated “special population” of nine patients received 40/12.5 (i.e., a reduced Betalutin dosage) due to low platelets and/or a previous autologous stem cell transplant. Part C was a small expansion cohort of four patients, all receiving the 40/15 regimen, and was designed to obtain supplementary pharmacokinetic data. Results: The efficacy analysis set comprised a total of 100 patients from the PARADIGME study. The overall response rates were 38.9% and 32.1%, and the complete response rates were 20.8% and 14.3% in the 40/15 and 100/20 groups, respectively. Correspondingly, the median response durations were 8.5 months and 3.4 months in the two groups. Hence, increasing the Betalutin activity dose by using the stronger protective CD37 pre-dosing (“100/20”) did not improve the therapeutic benefit. The most common grade ≥ 3 adverse events were hematologic, including neutropenia (11.5%) and thrombocytopenia (8.0%), with nadirs occurring around weeks 5–7 and recovery by week 11. Conclusions: A single-dose administration of Betalutin had a mild toxicity profile with a clinically relevant response rate. It represents a viable treatment alternative in FL patients who are not suitable for more toxic and long-lasting treatments. Trial Registration: This trial was registered at clinicaltrials.gov under #NCT 01796171.