Systemic toxicities*

11.1. IRRs
Work-up and evaluation: Physical examination including vital signs Pulse oximetry ECG if chest pain or sustained tachycardia
Grading	Management
G1: Mild transient reaction; infusion interruption not indicated; intervention not indicated.	Continue ICPi. May consider premedication with acetaminophen and an antihistamine for subsequent infusions.
G2: Therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medication indicated for ≤24 hours.	Consider holding ICPi temporarily and/or reducing the rate of infusion to 50% (or per institutional guidelines). Offer symptomatic treatment with antihistamines, NSAIDs, opioids, and IV fluids as clinicially appropriate. Offer prophylactic acetaminophen and an antihistamine per institution guidelines for subsequent infusions.
G3: Prolonged (eg, not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae.	Hold ICPi temporarily and consider resuming, at an infusion rate of 50% (or per institutional guidelines), once return to ≤G1. Offer symptomatic treatment with antihistamines, NSAIDs, opioids, and IV fluids as clinically appropriate. Consider antihistamines and corticosteroid medications IV. Hospitalization for other clinical sequelae.
G4: Life-threatening consequences; urgent intervention indicated.	Permanently discontinue ICPi. ICU-level inpatient care.
Additional considerations: Clinicians may consider switching to an alternate agent in the therapeutic class upon rechallenge or consider rechallenging with the offending immunotherapy agent through a desensitization procedure under the supervision of an allergist.

IRR: infusion-related reaction; ECG: electrocardiogram; ICPi: immune checkpoint inhibitor; NSAID: nonsteroidal antiinflammatory drug; IV: intravenous; ICU: intensive care unit.
* The American Society of Clinical Oncology (ASCO) guidelines are intended to provide initial guidance in the management of treatment-related side effects. Consultation with appropriate specialists may be indicated.

From: Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol 2021; 39:4073. DOI: 10.1200/JCO.21.01440. Copyright © 2022 American Society of Clinical Oncology. Reproduced with permission from Wolters Kluwer Health. Unauthorized reproduction of this material is prohibited.

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Systemic toxicities*