Evan J. Lipson, MD, Andrew Stolbach, MD, MPH, and Trish Brothers, BSN, RN, OCN®, prepared useful practice aids pertaining to oncologic emergencies for this CME/MOC/CNE/CPE activity titled "Urgent Care of Patients Receiving Cancer Immunotherapy: Recognition and Management of Immune-Mediated Adverse Reactions in the ED." For the full presentation, monograph, complete CME/MOC/CNE/CPE information, and to apply for credit, please visit us at http://bit.ly/2TGpnYl. CME/MOC/CNE/CPE credit will be available until February 21, 2020.

1. Recognizing and Managing Immune-Mediated Adverse Reactions Related to
Cancer Immunotherapies in the Emergency Department: Change Your Practice
PRACTICE AID
Access the activity, “Urgent Care of Patients Receiving Cancer Immunotherapy: Recognition and Management
of Immune-Mediated Adverse Reactions in the ED,” at PeerView.com/CBT40.
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice.
Change how you approach the evaluation, diagnosis, and management
of patients with cancer in the emergency department
IMARs: Immune-Mediated Adverse Reactions
A multidisciplinary approach can boost the collective awareness of IMARs and help keep patients safe
Ask about history of cancer
treatment, including
immunotherapy, from any
patient with cancer
presenting to an ED in
an acutely unwell state
History Consultation Diagnosis Management
Call the oncologist for any
moderate or severe
(grade 2 or higher) toxicity
upon presentation to
discuss treatment history,
if toxicity could be caused
by immunotherapy,
and next steps
Patients receiving
immunotherapies are
often given wallet cards
listing their therapies 
ask about that
Simplify treatment
decisions  consider
corticosteroids in front-line
management of
immune-related toxicities
in most cases
Coordinate with the
oncologist and other
specialists, if possible
Modify your differential
diagnosis when patient
has received cancer
immunotherapy  almost
any inflammatory condition
could be caused by immune
checkpoint inhibitor therapy
Avoid premature closure

2. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice.
Cancer immunotherapies are associated with important clinical benefits, but general immunologic enhancement
can also lead to a unique spectrum of immune-mediated adverse reactions (IMARs).
A multidisciplinary approach can boost the collective awareness of IMARs and help keep patients safe
Why do IMARs occur?
Any organ system can be affected; more commonly occurring are pulmonary (pneumonitis),
dermatologic(rash,pruritus,blisters,ulcers,vitiligo),gastrointestinal(diarrhea,enterocolitis,transaminitis,
hepatitis, pancreatitis), and endocrine (thyroiditis, hypophysitis, adrenal insufficiency) IMARs.
The precise pathophysiology is unknown,
but translational studies have shown that T-cell,
antibody, and cytokine responses may be involved.
Q A
A
Q
Pancreatitis,
autoimmune diabetes
Colitis
Enteritis
Encephalitis, aseptic meningitis
Thyroiditis, hypothyroidism,
hyperthyroidism
Dry mouth, mucositis
Hypophysitis
Uveitis
Pneumonitis
Thrombocytopenia,
anemia
Hepatitis
Adrenal insufficiency
Nephritis
Vasculitis
Arthralgia
Neuropathy
Rash, vitiligo
Myocarditis
How should IMARs be diagnosed and managed?Q
Increasing levels
of preexisting
autoantibodies
Enhancing
complement-mediated
inflammation due to
direct binding of an
anti–CTLA-4 antibody
with CTLA-4
expressed on
normal tissue
Activated T cell
Antithyroid
antibodies
Activated T cell
Anti–CTLA-4 antibody
CTLA-4 on pituitary Complement-
mediated
inflammation
Cytokines
Tumor with antigen
and activated T cells
What is the spectrum of potential IMARs?
General recommendations and management principles include the following:
IMARs are often diagnosed by exclusion; other causes should be ruled out (including adverse events from other therapies), but immunotherapy-related toxicity should always
be included in the differential.
There should be a high level of suspicion that new symptoms are treatment related; early recognition, evaluation, and treatment of IMARs are essential for patient safety and best outcome.
Depending on the severity of IMARs, management may require corticosteroid or other immunosuppressive treatment and interruption or discontinuation of therapy.
If appropriate immunosuppressive treatment is used, patients generally recover from IMARs.
Use of immunosuppressive therapy to manage IMARs does not affect response to immunotherapy.
A
Increasing T-cell
activity against
antigens that
are present in
tumors and
healthy tissue
Increasing
levels of
inflammatory
cytokines
Access the activity, “Urgent Care of Patients Receiving Cancer Immunotherapy: Recognition and Management
of Immune-Mediated Adverse Reactions in the ED,” at PeerView.com/CBT40.
Immune-Mediated Adverse Reactions Related to Cancer
Immunotherapies: Causes, Presentation, and Management1,2
PRACTICE AID

3. Access the activity, “Urgent Care of Patients Receiving Cancer Immunotherapy: Recognition and Management
of Immune-Mediated Adverse Reactions in the ED,” at PeerView.com/CBT40.
• In general, checkpoint inhibitor therapy should be continued with close
monitoring, with the exception of some neurologic, hematologic,
and cardiac toxicities
(Minimalornosymptoms;diagnosticchangesonly)
Grade 1
• Hold checkpoint inhibitor therapy for most grade 2 toxicities
• Consider resuming immunotherapy when symptoms and/or laboratory
values revert to grade 1
• Corticosteroids (initial dose of 0.5-1 mg/kg/day of prednisone or equivalent)
may be administered
Grade 3 toxicities:
• Hold checkpoint inhibitor therapy
• Initiate high-dose corticosteroids (prednisone 1-2 mg/kg/day or
methylprednisolone IV 1-2 mg/kg/day)
• If symptoms do not improve within 48-72 hours of high-dose
corticosteroid, infliximab may be offered for some toxicities
• Taper corticosteroids over the course of at least 4-6 weeks
• When symptoms and/or laboratory values revert to grade 1,
rechallenging with immunotherapy may be offered; however,
caution is advised, especially in patients with early-onset IMARs;
dose adjustments are not recommended
Grade 4 toxicities:
• In general, permanent discontinuation of checkpoint inhibitor therapy
is warranted, with the exception of endocrinopathies that have been
controlled by hormone replacement
Grade 2
(Mild to moderate symptoms)
(Severe or life-threatening symptoms)
Grades 3/4
CTLA-4: cytotoxic T-lymphocyte–associated protein 4.
1. Postow MA et al. NEnglJMed.2018;378:158-168.
2. Brahmer JR et al. JClinOncol. 2018;36:1714-1768.
Immune-Mediated Adverse Reactions Related to Cancer
Immunotherapies: Causes, Presentation, and Management1,2
PRACTICE AID