Cytokine Release Syndrome After CAR T Cell or Bispecific T Cell Engager Therapy in Multiple Myeloma

Patients with multiple myeloma receiving BCMA-targeted CAR T cells or bispecific T cell engagers are at risk of cytokine release syndrome (CRS), a potentially life-threatening systemic inflammatory response. Severity grading drives the clinical response, and grade 4 CRS represents the most critical presentation requiring immediate escalation.

Clinical scenario 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 in multiple myeloma. Grade 4 CRS demands rapid recognition and prompt, structured intervention.

Approach (partial overview) Severe CRS in this setting requires intensive supportive care alongside targeted immunomodulatory therapy. The structured protocol specifies the intervention sequence and defines escalation steps when initial therapy is insufficient. Full agent selection, sequencing, and escalation criteria are provided in the complete protocol below.

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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 4 CRS, the patient should be in the intensive care unit and receive tocilizumab and high-dose methylprednisolone (1 g/day); add anakinra if the CRS is unresponsive or even alternative agents such as etanercept [panel consensus; III, C].

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