PHRM 542 Oncology Supportive Care Immunotherapy ADEs and ICANS

Describe the general approach to treating mild immunotherapy related AEs (irAEs)

Continue immunotherapy

Manage symptoms

Describe the general approach to treating moderate irAEs

Consider pausing treatment and initiate corticosteroids (0.5-1 mg/kg/day)

Describe the general approach to treating severe irAEs

Discontinue therapy

Escalate to high dose steroids (1-2 mg/kg/day of prednisone) AND consider other immunosuppressive agents

Define cytokine release syndrome (CRS)

Caused by endogenous or infused effector cells, such as T cells, leading to a supra physiologic and rapid release of cytokines

Define immune effector cell-associated neurotoxicity syndrome (ICANS)

Thought to be due to diffusion of either the immune effector cells and/or cytokines through blood-brain barrier into the CNS

What are signs/symptoms of CRS?

Fever

Hypotension

Hypoxia

Tachycardia

What is the onset and duration of CRS?

Onset = 2-3 days after CAR-T

Duration = 7-8 days

What are signs/symptoms of ICANS?

Aphasia

Cognitive impairment

Seizures

Motor weakness

Cerebral edema

What is the onset of ICANS?

4-10 days after infusion

Define grade 1 CRS

Fever (above 38ºC)

Define grade 2 CRS

Fever, hypotension (not requiring pressors) and low O2

Define grade 3 CRS

Fever + low O2 + hypotension (requiring vasopressors)

Define grade 4 CRS

Fever + severely low O2 (intubation) + hypotension (multiple pressors)

Describe the treatment of grade 1 CRS

IV dexamethasone 10 mg q24h

Consider tocilizumab 8 mg/kg (max 800 mg)

IV fluids

Empiric broad spectrum antibiotics

Describe the treatment of grade 2 CRS

IV dexamethasone 10 mg q12-24h

Tocilizumab 8 mg/kg (max 800 mg) and may repeat in 8 hours if no response (max 3 times per day)

IV fluids

Empiric broad spectrum antibiotics

Vasopressors = admit ICU if needed

Describe the treatment of grade 3 CRS

ICU care

IV fluids and vasopressors

Empiric broad spectrum anitbiotics

IV dexamethasone 10 mg q6-12h

Tocilizumab 8 mg/kg (max 800 mg) and may repeat in 8 hours if no response (max 3 times per day)

Describe the treatment of grade 4 CRS

Same as grade 3

Mechanical ventilation

Dexamethasone q6h

Classify the grade of ICANS based on the ICE assessment tool

Grade 1 = 7-9 points

Grade 2 = 3-6 points

Grade 3 = 0-2 points

Grade 4 = PT unarousable

Describe the treatment of grade 1 ICANS with no concurrent CRS

Supportive care

Consider 1 dose of dexamethasone 10 mg IV and reassess

Describe the additional therapy for the treatment of grade 1 ICANS if concurrent CRS

Tocilizumab 8 mg/kg over 1 hour (not to exceed 800 mg)

Describe the treatment of grade 2 ICANS with no concurrent CRS

Supportive care

Consider 1 dose of dexamethasone 10 mg IV and reassess

Repeat Q6-12H

Describe the additional therapy for the treatment of grade 2 ICANS if concurrent CRS

Tocilizumab 8 mg/kg over 1 hour (not to exceed 800 mg) q8h prn max 3 doses/24 hours

Consider ICU if neurotoxicity associated with grade ≥ 2 CRS

Describe the treatment of grade 3 ICANS with no concurrent CRS

ICU care

Dexamethasone 10 mg IV q6h or methylprednisolone 1 mg/kg q12h

Describe the treatment of grade 4 ICANS with no concurrent CRS

ICU care (ventilation)

Dexamethasone 10 mg IV q6h or methylprednisolone 1 mg/kg q12h

Anakinra 100 mg q6h

Describe the additional therapy for the treatment of grade 3 and 4 ICANS if concurrent CRS

Same as grade 2 for IL-6