Practical Implications of Multi-Institution Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity (ICANS) Rates in Lymphoma Targeted Bispecific Antibodies (BsAb)

• Published in: Blood 2024-11, Vol.144, p.2350-2350
• Main Authors: Leidy, Sara, Snyder, Jordan, Davis, James A, Wesson, William, Hess, Brian, Jacobs, Ryan, Edmonds, Madalyn, Ahmed, Nausheen, Hoffmann, Marc
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-199658

Introduction Bispecific antibodies (BsAb) including epcoritamab, glofitamab, and mosunetuzumab are crucial options for the treatment of relapsed/refractory lymphoma. Known complications of BsAb therapy include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Currently hospitalization is required or should be considered for the initiation of BsAb therapy due to these associated risks. As these therapies continue to gain traction, practitioners seek to assess the safety and feasibility of outpatient administration and toxicity management. This study aims to offer real-world incidence of CRS/ICANS for lymphoma-directed BsAb therapy. Methods A multicenter review of adult patients who received commercial or investigational epcoritamab, glofitamab, or mosunetuzumab for non-Hodgkin's lymphoma from November 7th, 2022, to May 21st, 2024, was performed. The primary outcome was incidence of CRS/ICANS. Key secondary outcomes were surrogates for resource utilization including CRS/ICANS management strategies, level of care required, and hospitalization. Results Eighty-seven patients were included in the final analysis, of whom the median age was 69 (Interquartile Range [IQR], 61-79) with 57 (66%) patients being male. The most common diagnosis was that of diffuse large B cell lymphoma (56%), followed by follicular lymphoma (17%), marginal zone lymphoma (8%), Richter's transformation (7%), and mantle cell lymphoma (1%). Seventy-six (87%) patients had advanced stage disease and 6 (7%) of patients were identified to have central nervous system (CNS) involvement. Patients had a median of 4 prior lines (IQR, 3-5) of therapy, with 13 (15%) patients having received prior hematopoietic stem cell transplant and 35 (40%) having received prior chimeric receptor antigen T cell therapy. Sixty-three (72%) patients received commercial products and of the 3 available products, 28 (32%) received epcoritamab, 23 (27%) glofitamab, and 36 (41%) mosunetuzumab. All patients received standard steroid prophylaxis, with 37 (43%) of those patients receiving additional pre-medications. CRS occurred in 24 (28%) patients. Of these, 10 (28%) patients received mosunetuzumab, 9 (32%) epcoritamab, and 5 (23%) glofitamab. Grade 1 CRS was most common (18%) with grade 2 and 3 being 8% and 1%, respectively. For management of CRS, patients required steroids (14%), tocilizumab (10%), and vasopressors (1%). ICANS occurred in 6 (7%) patients, with 5 (83%) havin