Managing Grade 1 CRS in Patients With Follicular Lymphoma on Bispecific Antibodies: Home vs Health Care Facility Referred

Bispecific antibodies (BsAbs) have transformed the therapeutic management of follicular lymphoma (FL) and attract significant interest due to their broad accessibility. Two BsAbs are approved by the FDA for relapsed or refractory (R/R) FL: mosunetuzumab (Lunsumio; Genentech) and epcoritamab (Epkinly; AbbVie and Genmab).^1,2 Cytokine release syndrome (CRS) is a common adverse event (AE) during BsAb therapy. Although CRS can be serious, the majority of events reported in clinical trials and real‑world practice are often grade 1 (G1) and self‑limiting.³ These events may be safely managed in the outpatient setting, potentially reducing health care utilization and improving patient experience.^1,2

However, there is limited evidence to guide decisions about which cases can be safely treated at home and which require referral to a medical facility.³ This study aims to characterize real‑world management patterns of G1 CRS in patients with FL receiving BsAbs and to evaluate the impact of home management vs health care facility management on resource utilization and clinical outcomes.

Study Overview

We performed a retrospective cohort study across 8 US academic cancer centers participating in the Collaborative US Bispecifics Consortium. Eligible patients were 18 years or older with FL treated with commercial mosunetuzumab intravenously or epcoritamab subcutaneously between June 2022 and June 2025. Patients already hospitalized at the time of CRS onset were excluded from the G1 CRS subgroup analysis. Data were collected from electronic medical records and entered into an ad hoc database, including patient demographics; disease and treatment variables; response rates; and AEs, including CRS. Descriptive statistics were applied in the data analysis.

Study Results

We evaluated 88 patients with FL treated with either commercial mosunetuzumab (n = 83) or epcoritamab (n = 5) from June 2022 to June 2025. The median age was 68 years, 60% were male, and the median prior lines of therapy were 3 (Table 1).

Overall, only 1 immune effector cell–associated neurotoxicity syndrome event was reported, limited to G1. Any grade CRS occurred in 30 (34%) patients, with a total of 35 CRS occurrences. Consistent with the known CRS safety profile, most CRS events with mosunetuzumab occurred on cycle 1 day 15, whereas epcoritamab CRS events were observed on cycle 1 days 8, 15, or 22 (Figures 1 and 2). The majority of patients who developed CRS had a maximum CRS grade of 1 (n = 25; 83%), and 5 patients (17%) had grade 2 CRS. There were no reported grade 3 or higher CRS events. The median time to CRS onset and median duration of CRS were 1 and 2 days, respectively (Table 2).

Grade 1 CRS subgroup

Baseline characteristics were well balanced between home-treated and facility-referred cases in the grade 1 CRS subgroup (Table 3). There were 25 (24%) patients overall who developed G1 CRS. Four (16%) patients already hospitalized at the time of CRS were excluded from the subgroup analysis. Among the remaining cases of G1 CRS, one‑third (n = 8; 32%) were managed entirely at home, whereas more than half (n = 13; 52%) were referred to a health care facility. Of the health care facility-referred patients, 7 (54%) were then hospitalized for further management.

In facility‑managed cases, the patients underwent more diagnostic testing and received more interventions despite having similar CRS severity. Interventions included higher usage of steroids (13% vs 54%), tocilizumab (0% vs 8%), and empiric antibiotics (0% vs 46%), as seen in Figure 3. Only 1 patient with G1 CRS managed at home experienced a higher-grade CRS recurrence. In addition, 10 (77%) patients in the facility-referred group underwent infectious workups as part of their CRS assessment. Infectious workups were negative in all but 2 patients, who had viral infections.

Treatment efficacy remained similar regardless of management setting. In cases managed at home, patients had an overall response rate (ORR) of 100% and a complete response (CR) rate of 88%. In facility‑managed cases, patients had ORR and CR of 85% and 69%, respectively. 1‑year OS was 100% across all groups. Overall, there were no notable differences in CRS duration, recurrence, or response rates observed between home and facility-referred arms.

Conclusions and Key Takeaways

BsAb therapy is safe and tolerable for treatment of R/R FL, with most reported CRS events in our study being G1 (83%). Patients with G1 CRS who were referred to a health care facility for management had more utilization of corticosteroids, tocilizumab, empiric antibiotics, and resources for infectious workups. Nonetheless, survival was similar among patients treated in the home setting and those treated in a health care facility. There are several limitations to note in this study. Being that this is a retrospective analysis, therapeutic interventions, particularly at home, may have been underreported and were limited by the relatively small patient sample size.

However, our findings suggest that G1 CRS has the potential to be managed in the outpatient setting without a notable impact on clinical outcomes, while reducing health care resources and hospitalization time. Further studies on outpatient management of low-grade CRS are warranted. The complete analysis and results of this study will be reported in a forthcoming manuscript.

References

1. Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol. 2023;41(12):2238‑2247. doi:10.1200/JCO.22.01725

2. Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055‑1065. doi:10.1016/S1470-2045(22)00335-7

3. Crombie JL, Graff T, Falchi L, et al. Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy. Blood. 2024;143(16):1565‑1575. doi:10.1182/blood.2023022432