Real-world experience with management of CRS and ICANS following CD3xCD20 bispecific antibody therapy.

Abstract

e19015 Background: CD3xCD20 bispecific antibodies (BsAbs) have transformed treatment of relapsed/refractory B-cell lymphomas. Immune-mediated toxicities, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), remain challenging, with variable management. We characterized incidence, severity, timing, and management of CRS and ICANS. Methods: We performed a retrospective, single-center review of adult lymphoma patients treated with CD3xCD20 BsAbs at Mount Sinai Hospital between January 2021 and December 2024. CRS and ICANS were graded per ASTCT criteria. Exploratory comparisons between agents used Fisher’s exact test. CRS/ICANS-related mortality was defined as death with CRS or ICANS as the primary contributing cause. Results: Among 63 patients, 35 received glofitamab, 25 epcoritamab, and 5 mosunetuzumab. Median age was 65 years (IQR 57–73). Most patients had aggressive B-cell lymphomas (43/63, 68.3%), followed by indolent lymphomas (13/63, 20.6%) and other entities (7/63, 11.1%). CRS occurred in 35 patients (55.6%): grade 1 in 18 (28.6%), grade 2 in 13 (20.6%), and grade 3 in 4 (6.3%); no grade 4–5 events occurred. Grade ≥2 CRS occurred in 17 patients (27.0%). CRS incidence by agent was 60.0% with epcoritamab, 20.0% with mosunetuzumab, and 54.3% with glofitamab. All CRS and ICANS events occurred early after treatment initiation (median 1–3 days; range 1–7). Grade 1 CRS was managed with supportive care alone in 10 patients (55.6%), tocilizumab in 6 (33.3%), and corticosteroids in 2 (11.1%). For grade 2 CRS, tocilizumab and corticosteroids were each used in 10 patients (76.9%), with combination therapy in 9; supportive care alone was used in 2 patients (15.4%). All grade 3 CRS events were treated with tocilizumab and corticosteroids. ICANS occurred in 6 patients (9.5%): grade 1 in 1 (1.6%), grade 3 in 4 (6.3%), and grade 4 in 1 (1.6%). All ICANS cases occurred with concurrent CRS. ICANS incidence by agent was 14.3% with glofitamab (5/35), 4.0% with epcoritamab (1/25), and 0% with mosunetuzumab (0/5). All ICANS cases were treated with corticosteroids, and 5 patients (83.3%) received anakinra. There was a trend toward higher rates of grade ≥2 CRS and grade ≥3 ICANS with glofitamab; differences were not statistically significant (all p>0.05). Nine patients (14.3%) required ICU admission. Toxicity resolved in 32 of 35 patients (91.4%). CRS/ICANS-related mortality occurred in 3 of 35 patients (8.6%), all with aggressive B-cell lymphomas treated with glofitamab. Conclusions: CD3xCD20 BsAbs were associated with predominantly low-grade CRS and low ICANS incidence, with agent-specific differences. Severe CRS/ICANS requiring escalation was associated with ICU utilization and mortality, supporting standardized management pathways.