Immunotherapy Update Review of Immune Checkpoint Inhibitor and CAR T-Cell Therapy Adverse Effects and Treatments

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Cancer immunotherapy update Review of immune checkpoint inhibitor and CAR T-cell therapy adverse effects and treatments.

By Victoria L. Anderson, MSN, CRNP, FAANP, and Leslie Smith, MSN, RN, AOCNS, APRN-CNS

BECAUSE cancer treatment (surgery, radia- ments—immune checkpoint inhibitors and CNE tion, and chemotherapy) frequently fails, chimeric antigen receptor (CAR) T-cell thera- 1.5 contact hours research ers began asking why patients’ im- py—their immune-related adverse effects, mune systems don’t respond to cancer cells and treatment options. By understanding LEARNING like they do to bacteria and viruses. Under how these treatments work and their possible OBJECTIVES normal conditions, T lymphocytes (T-cells) adverse effects, nurses can better educate pa- 1. Describe how bind to a tumor cell via programmed cell tients and intervene quickly when necessary. immune check- death protein 1 (PD-1) and programmed point inhibitors death ligand 1 (PD-L1) receptors and then Immune checkpoint inhibitors and chimeric send signals that recruit antigen-presenting Immune checkpoint inhibitors (CTLA-4, PD-1, antigen recep- cells (APCs) that attach to the T-cells via and PD-L1) have emerged as potential targets tor (CAR) T-cell the cytotoxic T lympho cyte antigen-4 (CT- in the development of new cancer drugs. therapy work. LA-4) binding arm. Next, a series of cy- 2. Discuss adverse tokines (such as gamma interferon, inter- CTLA-4 inhibitors effects related leukin 12 and B7) work to kill the T-cell and Immune tolerance is the process described to immune the tumor cell through apoptosis (cell by Schwartz as an “anticipatory organ” that checkpoint in- death). Cancer tumor cells, however, block has learned to recognize self from nonself hibitors. T-cells from binding to dendritic cells, al- and prevent self-destruction through a series 3. Discuss adverse lowing the cancer to escape detection by of mechanisms that include T-cells, APCs, effects related the patient’s immune system. cellular receptors, and mediators. CTLA-4 is to CAR T-cell The U.S. Food and Drug Administration key in this process. therapy. (FDA) has approved several immunotherapy CTLA-4 is a receptor that competes for The authors and plan- agents to treat cancer. They help the immune binding with other receptors to regulate T-cell ners of this CNE activity have disclosed no system recognize tumor cells, prevent im- proliferation and inflammatory cytokine pro- relevant financial re- mune system tolerance of tumor cells, and duction. Intact CTLA-4 dampens inflammation lationships with any commercial companies manipulate translational proteins in the tu- and preserves immune tolerance, keeping the pertaining to this activi- mor microenvironment. However, these body’s immune response in check. Tumors ty. See the last page of the article to learn how drugs come with accompanying toxicities recognize the advantage of stimulating T-cells to earn CNE credit. (immune-related adverse effects). This article to express many CTLA-4 antigens on their Expiration: 9/1/23 focuses on two recently approved treat- surface and inhibit APCs from recognizing

6 American Nurse Journal Volume 15, Number 9 MyAmericanNurse.com and killing tumor cells. Anti-CTLA-4 mono- or delay of the immune checkpoint inhibitor clonal antibodies block CTLA-4, so that T- and the need for adjunctive treatments to cells can then destroy tumor cells. ameliorate its side effects. Ipilimumab is the only anti-CTLA-4 mono- Almost all adverse effects require treatment clonal antibody FDA-approved to treat cancer; with immunosuppression. Glucocorticoid ster- it’s indicated for advanced melanoma and re- oids are the primary drug of choice; however, nal cell and colon cancer. It is also used for other immunosuppressant agents may be used liver carcinoma, small cell lung cancer, and to regulate an overwhelming inflammatory re- esophageal cancer with orphan drug status. sponse caused by immune checkpoint in- Ipilimumab is used as an adjunct to alkylating hibitors. (See Adverse effect treatment options.) drugs like dacarbazine for mela noma and do- Organizational protocols are used for grad- cetaxel for renal cell cancer or in combination ing adverse effects, choosing treatment strate- with an anti-PD-1 drug. It’s administered I.V. gies, and determining whether immunothera- in a monitored setting. py will continue.

PD-1 and PD-L1 inhibitors Common adverse effects PD-1 in healthy tissue promotes self-tolerance; Common immune checkpoint inhibitor–related when deficient, it leads to autoimmune dis- adverse effects occur most frequently within eases. PD-L1 rarely occurs in healthy tissue, but the integument, endocrine, and GI systems, al- is present on cancer cells. It’s induced by the though less common effects can occur as well. production of the chemokine interferon gamma Integument. Skin rashes, vitiligo, and pru- by T-cells recruited to the tumor microenviron- ritis occur in more than 30% of patients receiv- ment. Interferon gamma initiates inflammation ing immune checkpoint inhibitor therapy. and PD-L1 expression. PD-1 on the T-cell binds Integument signs and symptoms generally to PD-L1 on the tumor surface, permanently mani fest early in ipilimumab and PD-1 inhibitor switching off T-cell recognition and preventing treatment. Rashes and pruritus usually can be T-cells from inducing tumor cell death and managed with topical glucocorticoid steroids causing immune fatigue. Monoclonal antibodies and don’t require immunotherapy suspension. have been developed that bind to PD-1 or PD- However, some patients who experience refrac- L1 to modulate immune suppression induced tory pruritus or Stevens-Johnson syndrome by the tumor in its microenvironment and re- (toxic epidermal necrolysis) may require an im- suscitate the patient’s immune system. mediate dermatology consultation and immunotherapy discontinuation. Immune checkpoint inhibitor–related Endocrine. The endocrine system is partic- adverse effects ularly vulnerable to CTLA-4 checkpoint inhibi- Immune checkpoint inhibitor disruption of tion but toxicities also can be seen in PD-1 and the tolerance of self vs. nonself leads to mul- PD-L1 therapy when combined with ipilimum- tiple organ system alterations. Before initiating ab. Patients show evidence of adverse effects therapy, providers should obtain a detailed related to ipilimumab typically after the sixth patient baseline history, perform a compre- or seventh week of treatment. Time to onset of hensive physical, and document findings in endocrinopathies caused by pembrolizumab is the electronic health record. 10 weeks and 11 weeks for nivolumab. Medi- Baseline lab tests include a complete meta- an onset can be between 1 to 5 months de- bolic panel, liver enzymes, complete blood pending on the drug. Endocrinopathies fre- count, thyroid levels, cortisol levels, baseline quently are permanent, and patients require scans, ECG, weight, and body mass index. As lifetime hormone replacement therapy. indicated by pre-existing conditions, echocar- Endocrine adverse effects include autoim- diograms, pulmonary function tests, pancreat- mune diabetes, thyroiditis, adrenal insufficien- ic enzymes, and musculoskeletal exams also cy, and hypophysitis. The decision to continue, should be performed. Monitoring the findings, hold, or discontinue immunotherapy after an obtaining detailed histories at each clinic visit, endocrine toxicity diagnosis depends on symp- and testing per patient status or clinical proto- tom severity, treatment response, and organiza- col can help identify adverse signs and symp- tion protocols and guidelines. toms for grading that determines continuation Autoimmune diabetes presents classically

MyAmericanNurse.com September 2020 American Nurse Journal 7 Adverse effect treatment options Several immunosuppressants are used to treat immune checkpoint inhibitor–related adverse effects.

Immunosuppressant Mode of action Indication

Anti-thymocyte globulin Destroys lymphocytes in secondary lymphoid tissue • Cardiac toxicity (myocarditis, pericarditis, and antigen-dependent cell-mediated cytotoxicity arrhythmias, ventricular dysfunction)

Azathioprine Inhibits DNA and RNA synthesis by interfering with • Inflammatory arthritis the precursors of purine synthesis and suppressing de novo purine synthesis; suppresses lymphocyte proliferation in vitro and production of IL-2, thereby inhibiting T-cell proliferation

Cyclophosphamide Alkylating agent is toxic to all human cells to differing • Renal toxicity degrees, with hematopoietic cells forming a particularly sensitive target

Cyclosporine Inhibits synthesis of ILs, including IL-2, which is • Hepatitis essential for self-activation of T-lymphocytes and • Renal toxicity their differentiation

Infliximab Blocks the interaction of tumor necrosis factor alpha • Enterocolitis and its receptors, inhibiting induction of pro- • Inflammatory arthritis inflammatory cytokines (IL-1, IL-6) and modulating • Pneumonitis the activity of immune effectors such as leukocytes, • Renal toxicity neutrophils, and eosinophils • Cardiac toxicity (myocarditis, pericarditis, arrhythmias, and ventricular dysfunction)

I.V. immunoglobulin-G Directly binds to natural antibodies, immuno- • Pneumonitis modulatory proteins (e.g., cytokines), or superantigens • Neurologic toxicity (Guillain-Barré and pathogens syndrome, myasthenia gravis, encephalopathy, transverse myelitis) • Inflammatory arthritis

Leflunomide Inhibits T-cell expansion • Inflammatory arthritis

Methotrexate Unknown in inflammation; may promote adenosine • Inflammatory arthritis (a natural anti-inflammatory) and may suppress • Ocular toxicities proinflammatory cytokines

Mycophenolate mofetil Immunosuppressive actions lead to decreased B- and • Liver, kidney, and pancreas toxicity T-cell proliferation, T-cell death, and dendritic cell and • Ocular toxicity (episcleritis, uveitis) IL-1 suppression • Pneumonitis

Rituximab Increases apoptosis of normal and malignant B cells • Inflammatory arthritis through complement and antibody-dependent • Encephalitis pathways

Sulfasalazine Unclear; anti-inflammatory effects may result from • Inflammatory arthritis inhibiting prostaglandins and arachidonic acid release

Tocilizumab IL-6 inhibitor • Inflammatory arthritis

IL = interleukin

with polyuria, polydipsia, polyphagia, weight Asymptomatic thyroiditis can be identified loss, and fasting glucose > 126 mg/dL. Auto- and monitored via laboratory test surveillance. immune diabetes diagnosis requires immedi- However, if a patient presents with clinical ate referral to an endocrinologist and may re- symptoms of hyperthyroidism (with palpita- sult in discontinuation of immune checkpoint tions, increased stool frequency, heat intoler- inhibitor therapy; if the diabetes can be con- ance, sweating, and weight loss) or hypothy- trolled, therapy can be resumed. roidism (with asthenia, constipation, dry skin,

8 American Nurse Journal Volume 15, Number 9 MyAmericanNurse.com hair loss, and weight gain) treatment is initiat- the eye. Adverse effects reported to the FDA ed as it would be for patients not receiving suggest more ocular toxicities are associated immune checkpoint inhibition therapy. with PD-1 and PD-L1 inhibitors. Life-threatening adrenal insufficiency can Referral to ophthalmology can confirm di- occur with or without central hypophysitis. agnosis and determine the degree of inflam- Arresting this adverse effect requires early di- mation. Mild inflammation typically can be agnosis and treatment. Typically, patients ex- treated with artificial tears; more significant ef- perience overwhelming fatigue, fever, visual fects may require topical and systemic corti- changes, myalgias, weakness, nausea, vomit- costeroids and immunotherapy delay or dis- ing, dizziness, and fainting. Their blood pres- continuation. sure is low, heart rate is elevated, and labora- Neurologic. The range of neurologic ad- tory tests may show low sodium and elevated verse effects includes peripheral neuropathy, potassium. Diagnosing central hypophysitis Guillain-Barré syndrome (GBS), myasthenia requires hypothalamic hormone (adrenocorti- gravis, aseptic meningitis, encephalopathy, cotrophic hormone, follicle-stimulating hor- and transverse myelitis. Immune checkpoint mone, luteinizing hormone, prolactin, anti- inhibitor therapy may be suspended depend- diuretic hormone, oxytocin, testosterone) ing on the severity of peripheral neuropathy testing; low levels suggest hypophysitis. Gen- and if a patient experiences GBS; therapy is erally, adrenal insufficiency, crisis, or hy- permanently discontinued when a patient ex- pophysitis triggers immune checkpoint in- periences aseptic meningitis, myasthenia hibitor therapy discontinuation. gravis, and transverse myelitis. GI. Enterocolitis related to immune check- GBS presents with symmetrical muscle point inhibitor therapy generally occurs 6 to 8 weakness, decreased or absent deep tendon weeks after initiating treatment and presents as reflexes, and thigh and watery diarrhea, abdominal pain and cramping, back pain. Some pa- nocturnal defecation, tenesmus, defecation ur- tients may also experi- Life-threatening adrenal gency, blood and mucus in stools, and fever. ence oculomotor, bul- The incidence of colitis is high in patients re- bar, facial, respiratory, insufficiency can occur with or ceiving ipilimumab and significantly higher or autonomic nerve without central hypophysitis. when ipilimumab is administered in combina- dysfunction. Treatment tion with nivolumab. Dehydration, weight loss, includes critical care and electrolyte disturbances may occur, requir- observation for airway management, auto- ing hospitalization for supportive care. Inflix- nomic dysfunction, and administration of cor- imab frequently is used to treat severe or glu- ticosteroids, I.V. immunoglobulin, or plasma- cocorticoid-resistant symptoms. pheresis exchange. Hepatitis and pancreatitis may occur suba- Myasthenia gravis presents with progres- cutely with abnormal liver or pancreatic en- sive or fluctuating muscle weakness (gener- zyme levels. Treatment includes glucocorticoids ally proximal to distal), ptosis, abnormal or mycophenolate mofetil. Infliximab is not a extraocular movements, double vision, dys- treatment of choice for hepatitis or pancreatitis. phagia, and facial muscle weakness; it also can be associated with myositis, myocardi- Less common adverse effects tis, and pneumonitis. Treatment includes Less common adverse effects of immune pyridostigmine 30 mg three times a day checkpoint inhibitor therapy occur in the oc- orally, gradually increased to a maximum ular, cardiovascular, pulmonary, neurologic, dose of 120 mg four times a day as tolerat- and musculoskeletal systems. ed. Depending on the patient’s symptoms, Ocular. Patients experiencing ocular tox- corticosteroids may be ordered; severe cas- icities may present with uvea or sclera in- es may require plasmapheresis and I.V. im- flammation. Commonly reported symptoms munoglobulin. include decreased visual acuity (blurred vi- Aseptic meningitis presents with sudden sion), trouble distinguishing colors, blind fever, severe headache, nausea or vomiting, spots, light sensitivity, and eye pain. Clini- double vision, drowsiness, sensitivity to bright cally, patients may have eyelid swelling, light, and neck stiffness. Encephalitis can be proptosis, or red or purple discoloration of characterized by fever, seizures, behavior

MyAmericanNurse.com September 2020 American Nurse Journal 9 How CAR T-cell therapy works Chimeric antigen receptor (CAR) T-cell therapy works by re-engineering a patient’s T-cells so they can recognize and kill cancer cells.

changes, confusion, and disorientation. Before are reported more frequently in patients receiv- treatment can be prescribed, infectious causes ing combination ipilimumab and nivolumab (which require appropriate antibacterial, anti- than in those receiving other immune check- fungal, or antiviral treatment) must be ruled point inhibitor therapies. These high-grade ad- out via lumbar puncture and lab tests. In the verse effects require immediate treatment with absence of infection, treatment includes cor - corticosteroids and I.V. immunoglobulin and tico steroids; for encephalitis, rituximab may immunotherapy discontinuation. be ordered. Continuing immune checkpoint Pulmonary. The most common pul- inhibitor therapy will depend on the toxicity monary adverse effect is pneumonitis, which level. occurs most frequently in patients receiving Transverse myelitis (spinal cord inflamma- PD-1 inhibitors. Patients with pneumonitis ex- tion) presents as rapidly progressing weak- perience dyspnea at rest, cough, decreased ness in the legs or arms. Pain and sensory al- oxygen concentration, and mental status teration as well as constipation, frequent or changes secondary to hypoxia. difficult voiding, incontinence, or partial or If pulmonary problems occur, immune complete extremity paralysis may occur. checkpoint therapy should be held and other Spinal magnetic resonance imaging, lumbar symptom causes excluded. Differential diag- puncture, and blood tests will rule out infec- noses can include a viral or bacterial respira- tion and detect antibodies associated with tory tract infection, pulmonary embolism, ab- immune causes. Treatment includes high- scess, or pneumothorax. Diagnostic tests dose corticosteroids, I.V. immunoglobulin, and include a chest computed tomography scan, plasmapheresis. sputum sample, or nasopharyngeal wash or Cardiovascular. Pericarditis, myocarditis, swab to rule out infectious causes. arrhythmias, and impaired ventricular function If mild symptoms and defects seen on im-

10 American Nurse Journal Volume 15, Number 9 MyAmericanNurse.com CAR T-cell organ system toxicities

Patients receiving chimeric antigen receptor (CAR) T-cell therapy may experience toxicity symptoms in all of their organ systems. aging resolve, immunotherapy can be restart- ed. Moderate to severe symptoms may require Cardiovascular Immunologic hospitalization for support, pulmonary consul- • Arrhythmias • Increased risk of viral, bacteri- • Decreased left ventricular al, and fungal infections tation, and treatment with oral or I.V. gluco- ejection fraction corticosteroids. Restarting immunotherapy for Musculoskeletal • Elevated troponins • Myalgias moderate to severe symptoms depends on ar- • Hypotension • Creatine phosphokinase resting symptoms, treating infections, and im- • QT prolongation elevation aging defect resolution without steroids. • Sinus tachycardia

Musculoskeletal. The incidence of inflam- Neurologic Constitutional matory arthritis and myositis in immune • Ataxia • Fatigue and malaise checkpoint inhibitor clinical trials ranges from • Cerebral edema • Fever • Cognitive disturbance 1% to 43%. Myositis (joint pain, stiffness, and • Headache swelling) is associated with inflammatory • Delirium, encephalopathy arthritis. Musculoskeletal adverse effects can GI and hepatic • Dysphasia occur with all immune checkpoint inhibitor • Diarrhea • Focal motor and sensory therapies, but a rare life-threatening myosi- • Elevated aspartate aminotrans- defects ferase, alanine aminotransfer - • Myoclonus tis is more commonly attributed to PD-1 and ase, alkaline phosphatase, or • Seizures PD-L1 therapies. direct bilirubin • Somnolence, obtundation Glucocorticoids are first-line treatment. For • Nausea, vomiting • Tremors patients whose symptoms don’t respond to glucocorticoids and immunotherapy discon- Hematologic Renal tinuation, other options include antitumor • Anemia • Hypokalemia • B-cell aplasia • Hyponatremia necrosis factor alpha drugs and interleukin 6 • Decreased fibrinogen • Hypophosphatemia inhibitors, as well as disease-modifying anti - • Disseminated intravascular • Increased serum creatinine rheumatic drugs (such as methotrexate, mino- coagulation • Renal insufficiency cy cline, hydroxychloroquine, sulfasalazine, or • Hemophagocytic lympho- • Tumor lysis syndrome azathioprine) in place of traditional inflamma- histiocytosis Respiratory tory arthritis drugs. • Hypogammaglobulinemia • Capillary leak syndrome Renal. Rare adverse effects can cause renal • Neutropenia • Dyspnea • Prolongation of partial throm- failure and acute kidney injury resulting from Hypoxia boplastin time or prothrombin • interstitial nephritis, which typically occurs 6 Increased respiratory rate time • to 12 weeks after initiating ipilimumab thera- • Pleural effusions • Thrombocytopenia py and 3 to 12 months after initiating nivolum- • Respiratory failure ab and pembrolizumab therapy. A one-and-a-half to two times increase of creatinine from baseline may be the first sig- nal of renal toxicity. Guidelines suggest as- CAR T-cell therapy sessing for and discontinuing any concomitant CAR T-cell therapy treats refractory, relapsed renal toxic drugs (for example, nonsteroidal B-cell malignancies by using the patient’s T- anti-inflammatories and diuretics) and per- cells re-engineered via a harmless virus carry- forming close surveillance. If creatinine rises ing the genetic material to recognize cancer- two to three times from baseline, the provider specific antigens for targeted cell killing. should hold immunotherapy and order corti- Patients who respond to this therapy have costeroids. Creatinine levels greater than four profound and enduring remissions. Research times from baseline are severe; immunothera- of CAR T-cell therapy in multiple myeloma, py, steroids, and other immunosuppressants leukemia, lymphoma, and solid tumors con- (such as azathioprine, monthly cyclophospha - tinues with some early reported successes. mide, cyclosporine, infliximab, or myco phen - CAR T-cell therapy begins with obtaining olate) should be discontinued. T-cells from the patient using leukapheresis. In addition to being aware of these adverse Large-bore venous access is required, and effects, keeping the possibility of pseudopro- many patients require a central line. Collected gression in mind is important when caring for T-cells undergo engineering and expansion in patients who are receiving immune checkpoint centers scrutinized by the FDA Center for Bi- inhibitors. ologics Evaluation and Research.

MyAmericanNurse.com September 2020 American Nurse Journal 11 Before receiving engineered cells, patients Nursing implications undergo lymphodepleting chemotherapy to Nurses have a pivotal and strategic role to play make space for the CAR T-cells and kill any in immunotherapy. They facilitate interdiscipli- residual cancer. Typical chemotherapy agents nary collaboration to educate patients and their used include cyclophosphamide and fludara- loved ones about treatment. When nurses un- bine. After completing chemotherapy, patients derstand each therapy’s symptom pathophysi- receive the engineered cells. (See How CAR T- ology, they can anticipate side effects, offer an- cell therapy works.) ticipatory guidance, and support patients and Two CAR T-cell products, tisagenlecleucel their families. Nurses also can diligently assess (Kymriah) and axicabtagene ciloleucel (Yes - for immune-mediated adverse effects and com- car ta), received approval through the FDA risk municate early with the team to initiate treat- evaluation and mitigation strategy to treat ment and avoid serious complications. When B-cell lymphomas and acute lymphoblastic nurses are familiar with a patient’s psychosocial leukemia. The cost of these therapies is and spiritual factors, they can help explore pal- around $500,000 per treatment. liative care and nonpharmacologic interven- tions such as reiki, acupunture, and massage. Adverse effects Through out treatment, nurses, as active mem- CAR T-cell therapy toxicities affect all organ bers of the healthcare team, can help patients systems. (See CAR T-cell organ system toxici- set reasonable expectations and clarify goals. ties.) Cytokine-release syndrome (CRS) is a Side effects can occur early in treatment or common life-threatening adverse effect. As re- present months after therapy ends, making it engineered T-cells move into the circulation, essential that at discharge patients and their inflammatory cytokines (cell messengers) re- caregivers understand what to look for and to lease pyrogens, vaso - call providers as soon as symptoms appear. dilators, and prosta - Nurses can reassure patients that side effects Nurses facilitate interdisciplinary glandins, which leads to don’t mean immunotherapy must stop. In collaboration to educate clinical manifestations most cases, if effects are managed early, treat- of fever, myalgias, rigor, ment can continue. patients and their loved ones hypotension, capillary Most organizations require that patients re- about treatment. leak, coagulopathies, and ceiving CAR T-cell therapy have a full-time hypoxia. Patients re- caregiver. Neurologic side effects of these drugs quire intensive care can be life-threatening, and caregivers who monitoring and ventilator support, and end-or- know a patient’s baseline neurologic status gan failure is common. Researchers’ discovery can call for help early. that a massive release of interleukin 6 occurs during CRS led to treatment with tocilizumab, Timely intervention an anti-interleukin-6 receptor antibody. If Providers and researchers are still learning tocilizumab isn’t effective, corticosteroids must about immunotherapy to treat cancer. be added, potentially jeopardizing CAR T-cell Nurses administering these agents should proliferation; however, this effect hasn’t been be familiar with their mechanisms of action proven. and adverse effects. Timely intervention The second most common adverse reaction can save a patient’s life and ensure treat- to CAR T-cell therapy is immune effector cell- ment continuation. AN associated neurotoxicity syndrome (ICANS), which presents with aphasia and confusion Visit myamericannurse.com/?p=67998 for references, a and can progress to loss of consciousness, co- list of FDA-approved PD-1 and PD-L1 inhibitors, and more information about pseudoprogression. ma, and seizures. ICANS frequently occurs in conjunction with CRS but is more likely to oc- Victoria L. Anderson is a senior nurse practitioner in the Labora- cur after CRS treatment. ICANS treatment is tory of Clinical Immunology and Microbiology, Immunopathogen- supportive with corticosteroids, airway man- esis Section at the National Institute of Allergy and Infectious Dis- agement, fall precautions, and one-to-one nurs- eases, National Institutes of Health (NIH) in Bethesda, Maryland. ing care. Research into drugs that block the in- Leslie Smith is a clinical nurse specialist in oncology, blood and flammatory interleukin 1 suggests its use may marrow transplant at the NIH Clinical Center Nursing Department help in severe ICANS cases. in Bethesda, Maryland.

12 American Nurse Journal Volume 15, Number 9 MyAmericanNurse.com

POST-TEST • Cancer immunotherapy update CNE: 1.5 contact hours CNE Earn contact hour credit online at myamericannurse.com/category/continuing-education/

Provider accreditation Contact hours: 1.5 The American Nurses Association is accredited as a provider ANA is approved by the California Board of Registered Nurs- of nursing continuing professional development by the ing, Provider Number CEP17219. American Nurses Credentialing Center’s Commission on Ac- Post-test passing score is 80%. Expiration: 9/1/23 creditation.

Please mark the correct answer 5. If that patient develops pericarditis, d. Many centers have received regen- online. which immunosuppressant might be erative medicine advanced therapy prescribed? designation so they can administer 1. Which statement about the function of CAR T-cell therapy to those who cytotoxic T lymphocyte antigen-4 (CTLA-4) a. Azathioprine need it. is correct? b. Cyclosporine a. CTLA-4 has no effect on the body’s c. Mycophenolate mofetil 10. Before patients receive CAR T-cell immune response. d. Anti-thymocyte globulin therapy, b. CTLA-4 increases the body’s re- a. durvalumab is administered. 6. The typical time frame when you would sponse to an infection. b. nivolumab is administered. c. CTLA-4 is a receptor that competes expect to see endocrine adverse effects related to ipilimumab is typically after the c. lymphodepleting chemotherapy is for binding with other receptors to discontinued. regulate T-cell proliferation and pro- a. second or third week of treatment. d. they undergo lymphodepleting duction of inflammatory cytokines. b. fourth or fifth week of treatment. chemotherapy. d. CTLA-4 is a receptor that competes c. sixth or seventh week of treatment. for binding with other receptors to d. eighth or ninth week of treatment. 11. Which of the following signs or symp- regulate B-cell proliferation and pro- toms would most indicate that your patient duction of inflammatory cytokines. 7. Which of the following statements who is receiving CAR T-cell therapy may about GI adverse effects related to immune have developed immune effector cell- 2. Ipilimumab is checkpoint inhibitor therapy is correct? associated neurotoxicity syndrome? a. one of five anti-CTLA-4 monoclonal a. Infliximab is not indicated for treat- a. Aphasia antibodies approved by the Food ment of severe GI symptoms. and Drug Administration. b. Hypotension b. Patients receiving ipilimumab have c. Myalgia b. contraindicated as an adjunct to a low incidence of GI symptoms. alkylating drugs used for melanoma d. Fever c. The incidence of GI adverse effects and renal cell cancer. is significantly higher with ipilimum- c. prescribed for oral administration. 12. A common treatment for cytokine- ab/nivolumab combination therapy. release syndrome is d. administered I.V. in a monitored d. Enterocolitis related to immune a. cemiplimab. setting. checkpoint inhibitor therapy gener- b. cyclosporine. ally occurs after 2 to 4 weeks. 3. Which statement about programmed c. azathioprine. death ligand 1 (PD-L1) is correct? 8. Your 71-year-old patient is receiving d. tocilizumab. a. PD-L1 is normally present in healthy atezolizumab for breast cancer. Which tissue and rarely present on cancer of the following would alert you to the 13. Which statement about pseudopro- cells. possibility of Guillain-Barré syndrome? gression is correct? b. PD-L1 is rarely present in healthy a. Hyper deep tendon reflexes a. It is unique to CAR T-cell therapy. tissue and is present on cancer cells. b. Decreased deep tendon reflexes b. It is unique to immune checkpoint c. Interferon gamma reduces inflam- c. Atypical myelitis inhibitors. mation and PD-L1 expression. d. Asymmetrical muscle weakness c. One theory of the mechanism of ac- d. Chemokine interferon gamma by tion is that erythrocytes invade the B cells stimulates PD-L1 production. 9. Which statement about CAR T-cell ther- tumor. apy is correct? d. Patients are typically rescanned 1 to 4. Your 45-year-old patient with non- a. It uses the patient’s T-cells re-engi- 2 years after pseudoprogression is small cell lung cancer who is receiving neered via a harmless virus carrying detected. pembrolizumab develops inflammatory the genetic material to recognize arthritis. Which immunosuppressant do cancer-specific antigens for targeted you anticipate the provider will prescribe? cell killing. a. Azathioprine b. It is used to treat refractory, relapsed b. Cyclosporine T-cell malignancies. c. Mycophenolate mofetil c. Remissions related to this therapy d. Anti-thymocyte globulin typically last 2 to 3 years.

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