Mosunetuzumab Associated With Improved Survival Among Patients With Relapsed or Refractory FL

Key Takeaways:

• High response rates: Among patients with relapsed or refractory follicular lymphoma (R/R FL), response rates to mosunetuzumab (mosun) were similar between trial-eligible and trial-ineligible patients.
• Manageable safety: While adverse events were infrequent and low in severity, trial-ineligible patients had higher rates of infection compared to trial-eligible patients.
• Treatment eligibility: These findings indicate that patients with high-risk R/R FL may still receive mosun, with physicians monitoring for infection.

Mosun is a bispecific antibody approved by the US Food and Drug Administration (FDA) to treat patients with R/R FL who have already undergone 2 lines of therapy. While mosun's clinical impact has been widely documented, its real-world safety and efficacy remains unclear, especially among patients unable to participate in clinical trials.

Researchers conducted a multicenter retrospective study of patients with R/R FL who were treated across 9 centers within the Collaborative US Bispecifics Consortium (CUBIC).

Patient Characteristics

The study identified 119 patients with non-Hodgkin lymphoma, 90 (75.6%) of which had indolent lymphomas. Among patients with indolent lymphomas, 20 (26%) were not eligible for the mosun registrational trial due to poor performance and cytopenias.

Ninety-seven percent of patients with indolent lymphomas received single-agent mosun. The remaining 3% received mosun in combination with another medication such as lenalidomide, cyclophosphamide, and rituximab.

Mosun Real-World Efficacy

Among patients with indolent lymphomas, the overall response rate (ORR) was 86%, and the complete response rate (CRR) was 71%. Responses were comparable among trial-ineligible patients, with an ORR of 78% and a CRR of 61%.

With a median follow-up of 17.0 months, a median progression-free survival (PFS) and overall survival (OS) was not reached. The PFS after 12 and 18 months was 70.5% and 56.7%, respectively. The OS estimates after 12 and 18 months were 95.3% and 92.9%, respectively. Rates of PFS and OS were similar between trial-eligible and trial-ineligible patients.

Mosun Real-World Safety

Treatment discontinuation was mainly due to therapy completion (61%) and disease progression (17%). Other reasons for treatment discontinuation included poor tolerance, recurrent infections, and second primary malignancy.

Cytokine release syndrome (CRS) occurred among 30 patients (33%), with 83% of cases being grade 1. Twelve patients did not require hospitalization, and their CRS was managed entirely in an outpatient setting.

Only 1 patient developed immune effector cell-associated neurotoxicity syndrome (ICANS), which had a grade 1 severity.

Infections occurred among 25 patients (27%). Common infections included Covid, pneumonia, rhinovirus or enterovirus, and sinusitis. Trial-ineligible patients had a higher rate of infections compared to trial-eligible patients, 45% vs 21%, respectively.

Of the 7 deaths that occurred during the study, 2 were due to disease progression, 2 because of cardiac etiology, 2 from “other causes,” and 1 due to second primary malignancy.

Implications for Managed Care

These findings illustrate that patients with high-risk R/R follicular lymphoma, particularly those with poor performance or cytopenias, should not be excluded from mosun therapy. Trial-ineligible patients demonstrated significant responses that were comparable to those of trial-eligible patients.

The authors noted that trial-ineligible patients had significantly higher rates of infection compared to trial-eligible patients, highlighting the importance of symptom monitoring and early intervention.

Reference

Jallouk AP, Falchi L, Chauhan A, et al. Real-World Outcomes of mosunetuzumab use in relapsed/refractory indolent lymphomas: a CUBIC consortium analysis. Blood Neoplasia. 2026:100280. doi: 10.1016/j.bneo.2026.100280