Grade 3 CRS in Multiple Myeloma After Grade 2 Management Fails to Maintain Blood Pressure
Cytokine-release syndrome (CRS) is a recognised complication in patients with multiple myeloma receiving CAR T cell or bispecific T cell engager therapy. When Grade 2 CRS management does not achieve haemodynamic stability, escalation to a Grade 3 CRS protocol is required.
Clinical scenario
Patient with multiple myeloma develops CRS following CAR T cell or bispecific T cell engager therapy. CRS is a systemic inflammatory response driven by T-lymphocyte activation, arising predominantly after BCMA-targeted CAR T cell or bispecific T cell engager treatment.
Previous line — escalation trigger
Grade 2 CRS management — incorporating intravenous fluid resuscitation and tocilizumab — targets maintenance of systolic blood pressure above 90 mmHg. When this haemodynamic threshold cannot be sustained despite those measures, the situation meets criteria for Grade 3 CRS management.
Grade 3 CRS — approach (partial)
Management at this grade escalates to intensive care support alongside a structured sequence of targeted immunosuppressive interventions, with further agents considered when the initial response is insufficient. The complete protocol — specifying agent selection, sequencing, and decision criteria — is available in full below.
References
DOI: 10.1038/s41571-025-01041-x
- CRS is a systemic inflammatory response mediated by the activation of T lymphocytes, observed mainly after treatment with BCMA-targeted CAR T cells or bispecific T cell engagers.
- For grade 3 CRS, consider intensive care, administer tocilizumab and add dexamethasone if there is no response within 24 h and increase the dose if refractory (to 20 mg intravenously every 6 h); add anakinra (2 mg/kg daily for 3–5 days) if the CRS is unresponsive; consider etanercept as clinically appropriate [panel consensus; III, C].