Fixed-Duration Subcutaneous Mosunetuzumab Shows Promising Efficacy in FL, MZL

Upfront treatment with fixed-duration subcutaneous mosunetuzumab demonstrated a high rate of complete response (CR) with limited toxicity in patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL), according to initial findings from the phase 2 BrUOG-401 study (NCT04792502).

“BrUOG-401 is an investigator-initiated study evaluating mosunetuzumab-based treatment in newly diagnosed follicular lymphoma and marginal zone lymphoma. It includes patients who achieve an early CR to mosunetuzumab complete fixed-duration monotherapy, and patients who are responding but who don’t achieve an early CR receive augmentation with low-dose lenalidomide,” study investigator Matthew Matasar, MD of Rutgers Cancer Institue and Rutger Robert Wood Johnson Medical School told Blood Cancers Today.

The study enrolled 37 patients to evaluate the hypothesis that administration of fixed-duration subcutaneous mosunetuzumab in previously untreated patients with FL and MZL could produce better responses compared to standard chemoimmunotherapy.

The patient population had a median age of 65 years (range, 30-89). Most patients were female (86%) and identified as non-Hispanic White. Of those enrolled, 22 (59%) had FL and 15 (41%) had MZL. Fourteen percent of patients had stage II lymphoma, 22% had stage III disease, and 64% had stage IV disease. The Follicular Lymphoma International Prognostic Index score in the FL cohort was low in six patients, intermediate in seven, and high in nine.

Patients were evaluated for the primary endpoint of CR rate. The secondary endpoints included safety, overall response rate (ORR), progression-free survival, overall survival (OS), and the rate of conversion from partial response to CR on mosunetuzumab combined with lenalidomide augmentation.

Of the 37 patients enrolled, 25 were evaluable for response. Per Lugano criteria, the CR rate observed was 82% (95% CI, 60%-95%), and the ORR was 86% (95% CI, 65-97%). The CR rates in the FL cohort and MZL cohorts were 80% and 86%, respectively.

For selective immune augmentation, six patients received lenalidomide, and three of the four evaluable patients achieved a CR. The fourth patient had progressive disease and histologic transformation. At a median of 5.8 months of follow-up, no patients with a CR showed disease recurrence. The OS rate observed was 100%. The efficacy findings met criteria for a pre-planned, two-stage study design.

Temporary decreases in circulating TEMRA CD8+ T-cells and a significant increase in LAG3 and PD-1 expression at cycle 2 were shown on flow cytometry. Moreover, following cycle 4, patients who did not achieve an early CR showed significantly lower counts of NK cells (P=.009) and no effector memory T-cell expansion. Investigators discovered that 4 cycles of mosunetuzumab plus lenalidomide augmentation settled the differences.

Discontinuation of study treatment ahead of cycle 8 occurred in two patients. In the remaining patients, the most common grade 1/2 adverse events (AEs) were treatment included injection site reaction (49%), fatigue (43%), and rash (38%). Grade 3/4 AEs included Pneumocystis jirovecii pneumonias, hypertension, weakness, pain, and neutropenia, and each occurred in two patients. Six patients (16%) had cytokine release syndrome, all of which were grade 1 in severity. Tocilizumab was administered to one patient. There were no grade 3/4 toxicities associated with lenalidomide treatment.

Investigators have determined that the use of low-dose continual lenalidomide for selective immune augmentation is safe and may assist with conversion to CR in patients who are slow to respond to mosunetuzumab. The study continues to enroll patients with FL and MZL, and long-term safety and efficacy analyses are ongoing.

“Enrollment and follow-up are ongoing, as are correlative biomarker studies,” said Matasar.

REFERENCE

Olszewski A, Matasar M, Huntington S, et al. Mosunetuzumab With response-driven lenalidomide augmentation as first-line therapy for symptomatic follicular or marginal zone lymphoma: interim analysis of a multi-center phase 2 study. Presented at: American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA. Abstract 1644.