Early Experience with Mosunetuzumab and Managing Cytokine Release Syndrome: Results of a Single Center Retrospective
Authors: Gill Victoria A , Raker Christina , Olszewski Adam J. , Reagan John L. , Pelcovits Ari 
Published: December 2024

Background
Mosunetuzumab (mosun) is a bispecific antibody (bsAb) approved for treatment of relapsed/refractory follicular lymphoma and is currently under investigation for several other indications. Like other bsAbs, mosun carries a risk of cytokine release syndrome (CRS), characterized by fever, hypotension, and hypoxia. No standardized model exists to predict patients (pts) at high risk for CRS, resulting in various mitigating practices including inpatient monitoring and pre-medication, patient education, and oncology staff support. The aim of this study was to evaluate our experience at an academic center with significant mosun experience, and to identify baseline characteristics associated with CRS risk, in hopes to inform best practices in diverse practice settings.
Methods
Pts receiving mosun (for any indication) from 1/1/2018 to 1/1/2024 at the Brown University Health Cancer Institute were identified for inclusion. Pt demographics and disease histology were collected, in addition to baseline laboratory data thought to be associated with CRS. Mosun and pre-medication administration (admin) details; including hospitalization for admin, was noted. Lastly, incidence, severity, and resolution of CRS was collected. A series of logistic regressions assessed correlation between pt and disease characteristics and CRS events.
Results
We identified 73 pts (DLBCL=48, HGBCL=8, FL=12, MZL=3, MCL=2). Median age was 74; 55% were female. Composition by self-reported race was 84% White, 15% Other/Declined, and 1% Black; 8 pts (11%) required interpreter assistance.
Forty-three (59%) pts received mosun intravenously (IV), the remainder subcutanously (SQ). Pts received mosun as monotherapy (n=35), with polatuzumab vedotin (n=27), with CHOP/CHP-based regimen (n=6), with lenalidomide (n=3), or with an experimental agent (n=2). Roughly half (53%) of pts were hospitalized for monitoring following their first admin, 16% for C2, and none for C3. Through C1, &gt;90% of pts received corticosteroid (CS), antihistamine (AH), and an antipyretic (AP) pre-medication. By C8, 38%, 60%, and 95% of pts continued to receive CS, AH, and AP pre-medication, respectively.
Twenty-one pts (29%) experienced a total of 26 CRS events. Incidents only occurred during C1 or C2, with most events in response to C1D1 (n=18, 69%). Most were Grade 1 (n=22); there were 3 G2 events and 1 G3 event. Three pts experienced recurrent CRS. There were no events in C3-C8, despite differences in pre-medication use, even among pts with a past CRS event.
Most (85%) CRS events were managed conservatively (i.e., acetaminophen, diphenhydramine, and/or IV fluids). Two pts required hospitalization for CRS following an outpatient admin of mosun, and 2 others required re-hospitalization after being discharged post-monitoring. Tocilizumab was used in only 2 cases, with 1 ICU stay. The median duration of CRS was 1 day (range, 1 to 3) and 76% of events resolved within 24h. There were no cases of ICANS.
As the bulk of CRS events occurred in response to the first admin, our logistic regression focused on that timepoint. Two statistically significant risk factors emerged: treatment naivety and concurrent medication administered. Pts who were treatment-naive had nearly 4x greater odds of CRS than those with 1+ prior lines of therapy (OR=3.87, p=.05). Pts who received CHOP concurrently had 22x greater odds than those receiving mosun as monotherapy (OR=22.1, p=.01). On the contrary, there was no observable difference in odds with co-admin of polatuzumab vedotin vs monotherapy (OR=1.0, p&gt;.99). Though non-significant, pts receiving mosun SQ had 54% lower odds of developing CRS compared to IV admin (p=.19).
No significant trends emerged from assessing sex, age, histology, stage, nor laboratory values. Directionally, we observed increased odds of CRS among pts with extranodal disease (OR=2.8, p=.08) and blood involvement of lymphoma (OR=2.5, p=.26), consistent with established risk factors.
Conclusion
In our experience, mosun carried a low risk of CRS (29%) and required little utilization of high-cost treatments like tocilizumab and ICU stays, which is reassuring for use in community practice. Our findings indicate that pts receiving mosun fist line and/or receiving CHOP concurrently have greater odds of CRS with the first admin; these factors should inform admin setting as mosun's role in a broader range of indications is revealed.