Outpatient Management of Grade 1 CRS Safe in R/R Follicular Lymphoma

Key Clinical Summary

• In a US multicenter retrospective study of 88 patients with relapsed or refractory (R/R) follicular lymphoma treated with bispecific antibodies, cytokine release syndrome (CRS) occurred in 34%, most commonly grade 1.
• Among patients with grade 1 CRS, outcomes—including CRS duration, recurrence, and response rates—were similar whether managed at home or referred to a health care facility.
• Facility-managed patients had higher use of steroids, tocilizumab, antibiotics, and infectious workups without clear differences in clinical outcomes.

Bispecific antibodies (BsAb) have expanded treatment options for R/R follicular lymphoma, but CRS remains a common adverse event. A multicenter US retrospective study evaluated whether patients with grade 1 CRS can be safely managed at home vs in a health care facility, with implications for resource utilization and care delivery.

Study Findings

The study included 88 patients with R/R follicular lymphoma treated with commercial mosunetuzumab (n = 83) or epcoritamab (n = 5) between June 2022 and June 2025. Median age was 68 years, 60% were male, and patients had received a median of 3 prior lines of therapy.

CRS occurred in 30 patients (34%). Of these, 25 (83%) experienced a maximum grade of 1, and 5 (17%) had grade 2 CRS. No grade 3 or higher events were reported. Median CRS onset was 1 day, and median duration was 2 days.

Among patients with grade 1 CRS, 8 (32%) were managed at home, 13 (52%) were referred to a health care facility, and 4 (16%) were already hospitalized. Of those referred to a facility, 7 patients (54%) required hospitalization.

Baseline characteristics were similar between outpatient-managed and facility-referred patients. However, facility-referred patients had higher rates of steroid use (53% vs 13%), tocilizumab administration (8% vs 0%), and empiric antibiotic use (43% vs 0%). Ten patients (77%) in the facility group underwent infectious evaluations; only 2 were found to have viral infections.

No significant differences were observed between home-managed and facility-referred groups in terms of CRS duration, recurrence, or treatment response.

Clinical Implications

For hematologists managing R/R follicular lymphoma with bispecific antibodies, these findings suggest that grade 1 CRS may be safely managed in the outpatient setting for appropriately selected patients. Avoiding unnecessary hospital referrals could reduce health care resource utilization, limit exposure to additional interventions, and potentially improve patient experience.

The higher use of steroids, tocilizumab, antibiotics, and infectious workups in the facility group did not translate into improved CRS-related outcomes. This may support more standardized criteria for outpatient monitoring of low-grade CRS, especially in centers with adequate patient education and follow-up infrastructure.

Given the increasing use of FDA-approved BsAb such as mosunetuzumab and epcoritamab in the US, practical guidance on CRS management is essential. Current practice often depends on institutional policies and clinician judgment; data-driven approaches could help refine triage decisions and optimize care pathways.

The investigators concluded that “BsAb therapy is safe and tolerable for treatment of R/R FL, with most reported CRS events being grade 1.” They further noted that grade 1 CRS “may be manageable in the outpatient setting without a notable impact on clinical outcomes while reducing healthcare resources and hospitalization time.”

Conclusion

In this US multicenter analysis, most CRS events associated with bispecific antibody therapy in R/R follicular lymphoma were grade 1 and self-limited. Outpatient management of grade 1 CRS appeared comparable to facility-based care in terms of outcomes, supporting potential resource-conscious care strategies.

Reference

Henshaw L, PharmD, Ahmed S, Salles G, et al. Outpatient versus inpatient management of grade 1 cytokine release syndrome in follicular lymphoma patients receiving bispecific antibodies: a cubic study. Transplant Cell Ther. 2026; 32(2): S459-S460. doi: 10.1016/j.jtct.2025.12.678