Risk factors for CRS and ICANS with Bispecific Antibodies for Aggressive Lymphomas
Bispecific antibodies (BsAbs) are effective treatments in aggressive B‑cell lymphomas but carry immune-mediated risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), particularly during the first cycle. We analyzed 255 patients receiving BsAbs across 14 institutions to identify predictors of CRS/ICANS. CRS occurred in 31% (Grade 3+: 5%) and ICANS in 8% (Grade 3+: 2%) of patients, with no significant differences across glofitamab, mosunetuzumab, or epcoritamab. CRS rates with glofitamab and epcoritamab as monotherapy were lower than reported in trials. In multivariable analysis, concurrent systemic chemotherapy was associated with Grade 2+ CRS, and the development of any-grade CRS and elevated ferritin independently was associated with ICANS. All patients with Grade 3+ CRS had very high serum C-Reactive Protein (sCRP, ≥15 mg/L) and elevated ferritin (>336 ng/mL) when available. These findings identify candidate laboratory thresholds and treatment related factors that warrant prospection validation for risk stratification and outpatient BsAb administration.
Authors
- Reem Karmali (ORCID: https://orcid.org/0000-0003-0984-4376)
- Thomas A. Ollila (ORCID: https://orcid.org/0000-0003-0102-6491)
- Jane N. Winter (ORCID: https://orcid.org/0000-0001-7542-3305)
- Jonathon Brett Cohen (ORCID: https://orcid.org/0000-0002-2723-6481)
- Leo I. Gordon (ORCID: https://orcid.org/0000-0003-1666-7064)
- Geoffrey Shouse (ORCID: https://orcid.org/0000-0002-7917-5713)
- Vaishalee Padgaonkar Kenkre (ORCID: https://orcid.org/0009-0000-4539-9332)
- Alexandra Noveihed (ORCID: https://orcid.org/0000-0002-0024-537X)
- Deborah Marie Stephens (ORCID: https://orcid.org/0000-0001-9188-5008)
- Brian T. Hess (ORCID: https://orcid.org/0000-0003-0176-2050)
- Jonathan Cruz Moreira (ORCID: https://orcid.org/0009-0001-9749-7599)
- Lindsey A. Fitzgerald (ORCID: https://orcid.org/0000-0001-5988-2878)
- Yun Kyoung Tiger (ORCID: https://orcid.org/0000-0002-8745-0906)
- Tamara Kay Moyo (ORCID: https://orcid.org/0000-0002-7431-8455)
- Megan Elizabeth Melody (ORCID: https://orcid.org/0000-0002-1923-1410)
- Adam Kidwell (ORCID: https://orcid.org/0009-0000-3961-4235)
- Natalie Sophia Grover (ORCID: https://orcid.org/0000-0002-1346-3157)
- Megan M. Herr (ORCID: https://orcid.org/0000-0001-5768-9396)
- Shuo Ma (ORCID: https://orcid.org/0000-0002-6139-5486)
- Narendranath Epperla (ORCID: https://orcid.org/0000-0002-8216-3457)
- James A. Davis (ORCID: https://orcid.org/0000-0001-7978-1652)
- Nirav Niranjan Shah (ORCID: https://orcid.org/0000-0002-4336-1071)
- Victoria Gill (ORCID: https://orcid.org/0009-0003-7431-3771)
- Ari Pelcovits
- Colin J Thomas
- Matthew J. Cortese
- Urmi Ghosh
- Adit Dharia
- Nicole Altomare
Institutions
- Rutgers, The State University of New Jersey (US)
- Northwestern University (US)
- University of North Carolina at Chapel Hill (US)
- Roswell Park Comprehensive Cancer Center (US)
- City Of Hope National Medical Center (US)
- Mayo Clinic (US)
- University of Wisconsin–Madison (US)
- Emory University (US)
- Medical University of South Carolina (US)
- Medical College of Wisconsin (US)
- University of Utah (US)
- Brown University (US)
- Huntsman Cancer Institute (US)
- Tampa General Hospital (US)
- Levine Cancer Institute (US)
- City of Hope (US)
- University of Kansas Medical Center (US)
- AdventHealth Tampa (US)
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
- UNC Lineberger Comprehensive Cancer Center
- University of Pennsylvania (US)
Publication Details
- Journal
- Blood Advances
- Published
- 2026-09-24
- DOI
- https://doi.org/10.1182/bloodadvances.2026020595
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00