practice aid understanding car-t therapy: a guide for

Access the activity, “Navigating the CAR-T Cell Therapy Landscape in Hematologic Malignancies: Science and Practical Issues in Nursing Care,” at PeerView.com/CARTnurse19.

Understanding CAR-T Therapy: A Guide for Oncology Nurses

PRACTICE AID

It is a treatment for relapsed or refractory cancers using patient-derived T cells that are genetically modi�edto target cancer antigens on the surface of malignant cells; CAR-T cell therapy has shown promise inpatients in the leukemia, lymphoma, and myeloma settings

What is CAR-T cell therapy?1

Treatment Process

Genetic modi�cation of theT cells using viral vector

CAR-T cellexpansion

Infusion

Blood istaken fromthe patient

T cells aresent tothe lab

In the ClinicCAR-T cells are infused back into the patient's bloodstream,typically after lymphodepleting chemotherapy; the CAR-Tcells continue to multiply

The receptors are attracted to the targets

on the surface ofthe cancer cells

Target

Dying cancer cell

Cancer cell

CAR-T cellIn the Body

The CAR-T cells identify targetantigens (eg, CD19, BCMA)on the cancer cells and kill

them; CAR-T cells may remainin the body for some time, thus

preventing relapse

Virus

T cellReceptor

In the Lab/Manufacturing FacilityT cells are engineered using a lentiviral or retroviral vector

An inactive virus is usedto insert genes into the T cells

The genes cause the T cellsto make receptors, calledCARS, on their surfaces

2

4

3

ScreeningLeukapheresis

Modi�ed T cells (now calledCAR-T cells) are multiplied

Blood

In ApheresisThe white blood cells, including T cells, areseparated out, and the rest of the blood isreturned to the patient

1

Manufacturing Process

Enrollment



PRACTICE AID

CAR-T cell therapies are used or under investigation in which cancer settings?

Axicabtagene ciloleucel(KTE-019)6

Adult patients with relapsed/refractory large B-cell lymphoma

after two or more lines ofsystemic therapy

FDA approved

Tisagenlecleucel(CTL019)2

Adult patients with relapsed/refractory large B-cell lymphoma

after two or more lines ofsystemic therapy

FDA approved

Lisocabtagene maraleucel(JCAR017)7,8

Relapsed/refractory DLBCL(phase 2); relapsed/refractory

CLL/SLL (phase 1/2)

Breakthrough therapy designation

B-Cell NHL(Anti–CD19-Targeted CAR-T Cell Therapy)

ALL(Anti–CD19-Targeted CAR-T Cell Therapy)

Tisagenlecleucel(CTL019)2

Patients aged ≤25 y withB-cell precursor ALL (refractory

or in second or later relapse)

FDA approved

Axicabtagene ciloleucel(KTE-019)3,4

Adult/pediatric relapsed/refractoryB precursor ALL after two

or more lines of systemic therapy

Phase 1/2

Lisocabtagene maraleucel(JCAR017)5

Pediatric and young adultrelapsed/refractory B cell ALL

Phase 1/2

Myeloma(Anti–BCMA-Targeted CAR-T Cell Therapy)

Phase 1

bb21219

Phase 1

bb2121710

Phase 1b/2

LCAR-B38M11

Phase 1/2

JCARH02512

Phase 1

P-BCMA-10113

Phase 1

MCARH17114

Phase 1

FCARH14315

Adult relapsed/refractory multiple myeloma



PRACTICE AID

This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.

ALL: acute lymphoblastic leukemia; BCMA: B-cell maturation antigen; CAR: chimeric antigen receptor; CD19: cluster of differentiation 19; CLL: chronic lymphocytic leukemia; DLBCL: diffuse large B cell lymphoma; NHL: non-Hodgkin lymphoma; SLL: small lymphocytic lymphoma; TCR: T cell receptor.

1. Wang X, Rivière I. Mol Ther Oncolytics. 2016;3:16015. 2. Kymriah (tisagenlecleucel) Prescribing Information. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kymriah.pdf. Accessed March 17, 2019. 3. Wierda WG et al. 2018 Annual Meeting of the American Society of Hematology (ASH 2018). Abstract 897. 4. Lee DW et al. European Society for Medical Oncology 2017 Congress (ESMO 2017). Abstract 1008PD. 5. https://www.clinicaltrials.gov/ct2/show/NCT03743246. Accessed March 17, 2019. 6. Yescarta (axicabtagene ciloleucel) Prescribing Information. https://www.yescarta.com/wp-content/uploads/1-pi.pdf. Accessed March 17, 2019. 7. Abramson JS, et al. 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO 2018). Abstract 7505. 8. Siddiqi T et al. ASH 2018. Abstract 300. 9. Raje N et al. ASH 2018. Abstract 8007. 10. Shah N et al. ASH 2018. Abstract 488. 11. Zhao WH et al. J Hematol Oncol. 2018;11:141. 12. Mailankody S et al. ASH 2018. Abstract 957. 13. Gregory T et al. ASH 2018. Abstract 1012. 14. Mailankody S et al. ASH 2018. Abstract 959. 15. Green DJ et al. ASH 2018. Abstract 1011.

What is the role of the oncology nurse in the clinical application of CAR-T cell therapy?

Role ofOncologyNurses in

CAR-T CellTrial Programs

Expedite eligibilityscreening

for CAR-T trialcandidates and review

documents todetermine eligibility

Communicate withpatients and referring

team regardingeligibility review and

insurance approval andsecure appointments

for variousprocedures

Provide patienteducation regarding

CAR-T cells, treatment process,

and safetymanagement

Establish patientcare plan basedon established

guidelinesfor patient

management

Manage infusionof CAR-T cells

Closely monitor forand promptly

respond to toxicities;CAR-T cell toxicity

managementrequires complex

nursing care

Follow patientsin the inpatientand outpatient

settings

Collect clinical trialand research data


Managing Unique Toxicities Associated With CAR-T Cell Therapy: A Guide for Oncology Nurses1-6

PRACTICE AID

General Guidance

Determine toxicity

Grade toxicity

Manage toxicity

¨ Symptoms: constitutional �u-like symptoms, hypotension, tachycardia, cardiac events, hypoxia, renal insu�ciency, multiple organ failure¨ Very frequently begins with fever, with severe CRS often progressing to unstable hypotension¨ May require ICU-level care; can be fatal

ASBMT Toxicity Criteria by Grade

¨ Manage toxicities by clinical symptoms and progression¨ Symptom management; maintenance of �uids; antipyretics, analgesics (often narcotics), antiemetics, blood products, O2, vasopressin early in treatment of hypotension, anti–IL-6 therapy (tocilizumab), corticosteroids; CPAP, ventilation; transfer to ICU

Temperature

Hypotension

Hypoxia

≥38° C

None

None

1≥38° C

Not requiringvasopressors

Requiringlow-�ow nasal

cannula orblow-by

2≥38° C

Requiring avasopressor

± vasopressin

Requiringhigh-�ow nasal

cannula, facemask,nonrebreather

mask, orventuri mask

3≥38° C

Requiringmultiple

vasopressors(but not

vasopressin)

Requiringpositive pressure(eg, CPAP, BiPAP,

intubation,and mechanical

ventilation)

4

Cytokine Release Syndrome (CRS)



PRACTICE AID

Neurological Toxicities (ICANS)

¨ Vary by CAR-T cell product¨ Symptoms: aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral edema¨ Increase in ICP occurs—can progress to cerebral edema, which can be rapid in onset and life-threatening

ASBMT Toxicity Criteria by Grade

¨ Supportive care; neurologic work-up; NPO as appropriate; neuroimaging; anxiolytics and/or antiepileptics (levetiracetam) as needed; anti–IL-6 therapy (tocilizumab or siltuximab); early use of corticosteroids¨ Transfer to ICU¨ Often self-resolving with the exception of cerebral edema, which is a medical emergency

ICE score (patients aged >12 y)

CAPD score(patients

aged ≤12 y)

Level ofconciousness

Seizure

Motor weakness

ICP/Cerebral edema

7-9

<9

Awakensspontaneously

N/A

N/A

N/A

13-6

<9

Awakensto voice

N/A

N/A

N/A

20-2

<9

Awakens onlyto tactilestimulus

Any clinical seizure(focal or generalized)

resolving rapidlyor nonconvulsive

seizure on EEGthat resolves

with intervention

N/A

Focal/localedema on

neuroimaging

30 (unable toperform ICE)

Unable to perform CAPD

Unarousable orarousable only

with vigorous orrepetitive tactilestimuli; stupor

or coma

Life-threateningseizure >5 min orrepetitive clinical

or electricalseizures with no

return to baselinein between

Deep focal motorweakness

(eg, hemiparesis,paraparesis)

Decerebrate ordecorticate

posturing, cranialnerve VI palsy,papilledema,

Cushing's triad,di�use cerebral

edema onneuroimaging

4



PRACTICE AID

This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.

ASBMT: American Society for Blood and Marrow Transplantation; BiPAP: bilevel positive airway pressure; CAPD: Cornell Assessment of Pediatric Delirium; CAR: chimeric antigen receptor; CPAP: continuous positive airway pressure; CRS: cytokine release syndrome; EEG: electroencephalogram; ICANS: immune effector cell–associated neurotoxicity syndrome; ICE: Immune Effector Cell–Associated Encephalopathy score; ICP: intracranial pressure; IL: interleukin; NPO: nothing by mouth.

1. Neelapu SS et al. Nat Rev Clin Oncol. 2018;15:47-62. 2. Kymriah (tisagenlecleucel) Prescribing Information. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kymriah.pdf. Accessed March 17, 2019. 3. Yescarta (axicabtagene ciloleucel) Prescribing Information. https://www.yescarta.com/wp-content/uploads/1-pi.pdf. Accessed March 17, 2019. 4. Howard SC et al. Ann Hematol. 2016;95:563-573. 5. Lee DL et al. Blood. 2014;124:188-195. 6. Lee DW et al. Biol Blood Marrow Transplant. 2018 Dec 25. [Epub ahead of print].

B-Cell Aplasia

Expected result of successful CD19-speci�c CAR-T cell treatment

Immunoglobulin replacement therapymay be given to prevent infection

Tumor-Lysis Syndrome

Metabolic complications from breakdown of dying cells; can cause organ damage and

may be life-threatening

Monitor for hyperkalemia,hypocalcemia, and elevated uric acid;provide standard supportive therapy

Anaphylaxis

Symptoms: hives, facial swelling,tingling hands, low blood pressure,

hypoxia, and respiratory distress

Thorough monitoring andimmediate treatment are critical

practice aid understanding car-t therapy: a guide for

Documents