Recap: Mitigation of CRS and ICANS During Bispecific Treatment in Multiple Myeloma

CancerNetwork^® hosted a Training Academy program focused on monitoring cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) for patients with multiple myeloma who have been treated with bispecific agents.

Adverse Effects Experienced

• CRS
  • CRS is triggered by activation of T cells and can cause fever, myalgia, low blood pressure, and tachycardia.
  • CRS usually occurs during the first week of treatment.
  • Intervention typically begins at grade 1 CRS and is treated with tocilizumab (Actemra).
  • Risk factors for CRS include low blood pressure, hypoxia, or evidence of organ toxicity.
• ICANS
  • Dexamethasone is used as first-line treatment for ICANS. Anakinra (Kineret) is used in the second line.
  • Prophylactic antiepileptic drugs can be utilized when neurological symptoms are noticed.
  • Narcotics can be used to manage tumor flare, as can dexamethasone if the pain does not respond to the original treatment.

Key Pieces of Information

• Educating the patient is important so they can accurately report any adverse effects they experience.
• Communication between the pharmacy and the floor nurse needs to be effective so tocilizumab can be administered early.
• Utilizing the ICAN encephalopathy (ICE) test will help to determine if there are any neurological deficits.

Grading of CRS and ICANS

CRS

• Grade 1
  • Temperature above 38 °C
• Grade 2
  • Temperature above 38 °C
  • No need for vasopressors
  • Needs a low-flow nasal cannula
• Grade 3
  • Temperature above 38 °C
  • Needs 1 vasopressor with or without vasopressin
  • Needs a high-flow cannula, face mask, non-rebreather, or Venturi mask
• Grade 4
  • Temperature above 38 °C
  • Needs multiple vasopressors
  • Requires positive pressure like CPAP, BiPAP, intubation, or mechanical ventilation

ICANS

• Grade 1
  • ICE score between 7 and 9
  • Awakens spontaneously
• Grade 2
  • ICE score between 3 and 6
  • Awakens to voice
• Grade 3
  • ICE score between 0 to 2
  • Awakens only to tactile stimulus
  • Experienced any clinical seizures that are resolved quickly; or nonconvulsive seizures on EEG that are resolved with the intervention
  • Focal/local edema observed on imaging
• Grade 4
  • ICE score 0
  • Patient cannot be awakened or requires vigorous and numerous tactile stimuli
  • Seizures longer than 5 minutes; or repetitive clinical seizures without a return to baseline in between
  • Deep focal motor weakness
  • Diffuse cerebral edema on the neuroimaging; decerebrate or decorticate posturing; or cranial nerve VI palsy; papilledema; or Cushing’s triad

Reference

1. Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758