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CAR T-CELL THERAPIES:

NURSING IMPLICATIONS

Neena Kennedy, RN, BSN

Clinical Research Nurse

Deptartment of Hematology and Hematopoietic Cell Transplantation

How the Experts Treat Hematologic Malignancies

Las Vegas, NV

March 11, 2016

Elizabeth Budde, MD, PhD

Assistant Professor

Department of Hematology & Hematopoietic Cell Transplantation Member

Toni Stephenson Lymphoma Center

Department of Hematology and Hematopoietic Cell Transplantation

DISCLOSURES

• Kennedy – no disclosures

• Budde – no disclosures

OBJECTIVES

• Nursing implications of giving CAR Tcells

• Preview of Cytokine Release Syndrome

• Patient/family education regarding CAR Tcell therapy

Introduction

• Many novel immunotherapies in the industry.

• CAR T-cells becoming more common. Many clinical trials,

new pharmaceutical companies offering T-Cell therapies.

Study Schema

Study Schema:

Leukapheresis Lymphodepleting

Chemotherapy

CAR T-cell

Infusion

Leukapheresis

• Leukapheresis (Tcell collection) can be done peripherally

or with Hickman catheter (no port or PICC).

• Important to have experienced apheresis nurses perform

vein assessment to determine need for Hickman.

• Leukapheresis done in a one-time run,

• usually over 4-6 hours, study specific.

• After collection, patient’s T-cells are then genetically

modified and expanded in a lab.

• This process takes 2-4 weeks.

Lymphodepletion

• The lymphodepletion regimen depends on the sponsor and

the protocol.

• Cyclophosphamide alone generally given over 2 days.

• or Cyclophosphamide and Fludarabine together:

» usually given over 3 days

• The goal of lymphodepletion is to shut down the patient’s

endogenous immune system

• which allows the genetically modified cells to react and

expand.

T-Cell Infusion: Step-by-Step

• Day of T-cell infusion.

– Patients are pre-medicated with Benadryl and Tylenol.

– NO systemic steroids are to be given after the Tcells

are infused.

– The length of time the patient must be steroid free

depends on the sponsor and the protocol.

– Steroids can diminish or ablate the genetically modified

T-Cells.

At City of Hope

• At City of Hope we

have a No Steroid

alert put into our

electronic system.

• We also use old

fashioned visual aids!

T-Cell Delivery Protocols

How are Genetically Modified T-cells given?

The industry is too new, there is no standard

Varies according to study, sponsor and the protocol

T-Cell Preparation

The T-Cells can be:

• Frozen and thaw at the bedside like stem cells

(water bath)

• Thaw at room temperature

• Infused by gravity

• Infused on a pump

• Given as a slow IVP

T-Cell Water Bath Thaw

• The T-cells may be in 1 bag or

multiple bags

• This depends on the dose level

of T-Cells to be given and the

manufacturing platform

Administration

RISK

Patients receiving multiple bags

of T-Cells are at the same

DMSO risk as patients receiving

stem cells:

• Garlic taste or smell

• BP changes

• Chills

• N/V

• Dyspnea

Post-Procedure Care

• Required Observation for CRS is protocol dependent.

• Some studies require the pts to be seen daily as an

outpatient.

• Some studies require mandatory inpatient admit to receive

their T-Cells.

• Day of infusion is frequently uneventful.

• We always request 1:1 bedside nursing for frequency of

vital signs, diligent assessment.

Cytokine Release Syndrome (CRS)

CAR T-Cell therapy can result in:

Cytokine Release Syndrome (CRS)

Symptoms present much like sepsis:

• Fever

• Hypotension

• Tachycardia

• Oxygen desaturation

• Rash

• Altered Mental Status

CRS Symptoms

• Cytokine Release Syndrome can be:

• Mild: High fevers lasting up to a week, hypotension

responding to fluid bolus and supportive care.

• Severe: ICU admission requiring intubation and

vasopressor support

• And everything in between

• Historically CRS can occur within the first 4-12 days,

but can occur at any time.

CRS Symptoms, continued

• IL-6 is significantly elevated during CRS.

• C-Reactive Protein (CRP) is a surrogate

marker for IL-6 since IL-6 is not a readily

available lab test. We normally monitor CRP

levels daily for first 1-2 weeks post T-Cells.

• Tocilizumab is an IL-6 receptor antagonist, and is

first line treatment of severe CRS

• Used to treat:

• Juvenile Idiopathic Arthritis

• Rheumatoid Arthritis

• Tocilizumab can reduce the effects of IL-6

CRS Treatment Options

Cytokine Release Syndrome

For more information on

Cytokine Release Syndrome

attend the lecture on

Saturday morning

T-Cell Therapy

• CAR T-Cell therapy targeting CD19 is known to

cause neurotoxicity

Symptoms mimic a stroke

• Aphasia

• Weakness

• Confusion

• Obtunded

Neurotoxicity

• Neurotoxicity can occur during the onset of CRS or later

• Thus far, all reported neurotoxic effects have been

reversible

• Neurotoxic effects frequently take longer to resolve than

other CRS symptoms

For Patients and Family

– Patient and Family Education (title stays the same)

– Educate Patient and Family to watch for Adverse Events

• Fever

• Chills

• Dyspnea

• Immediately alert bedside nurse of any new symptoms

– Family is first line in noticing changes in mental status as

they know their family member best

T-Cell Clinical Trials

CAR T-Cell clinical trials currently at City of Hope:

ALL – Adult patients (Pediatric is opening soon)

AML

Non-Hodgkin Lymphoma (DLBCL, FL)

NHL (in conjunction with Autologous HCT)

MCL

Multiple Myeloma (opening later 2016)

Glioblastoma

QUESTIONS??