immuno-oncology: how to develop a treatment plan · 1. learner will identify potential treatment...

Oncology Nursing Society 43nd Annual CongressMay 17–20, 2018 • Washington, DC 1Preconference

Karen Anderson, MN, RN, AOCNS, BMTCN, CRNIClinical Operations ManagerBezos Family Immunotherapy Clinic Seattle Cancer Care Alliance [email protected]

Abigail Baldwin-Medsker, MSN, RN, OCNMemorial Sloan Kettering Cancer Center [email protected]

Key Session Takeaways1. Learner will identify potential treatment plan options for patients

receiving immune-oncology. 2. Learner will identify two potential toxicities of CAR T-cell thera-

py and management strategies. 3. Learner will describe nursing considerations for a patient with

financial toxicity.

Immuno-Oncology: How to Develop a Treatment PlanWednesday, May 16 • 3:30–5:30 pm

Note one action you’ll take after attending this session: ____________________________________________________

________________________________________________________________________________

ONS 43rd Annual Congress

Preconference 1

ONS Pre ConferenceImmuno-Oncology: How To Develop a Treatment Plan

Karen Anderson MN, RN, AOCNS, BMTCN, CRNI

Abigail Baldwin-Medsker MSN, RN, OCN

Disclosures

No disclosures


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Key Takeaways • Learner will identify potential treatment plan options for

patients receiving immune-oncology.

• Learner will identify two potential toxicities of CAR T cell therapy and management strategies.

• Learner will describe nursing considerations for a patient with financial toxicity.

Cancer is smart, but your immune system is smarter.

The body’s own immune system provides one of the

best defenses against cancer.

Presentation Overview: How to Develop a Treatment Plan

• Definition of Immunotherapy• Historical perspective & The Paradigm Shift• Immuno-Oncology (IO) • Symptom & Toxicity Profiles • Safe Handling • Patient and Caregiver Considerations• Financial Implications• Implications to Nursing Practice & the Future


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Immunotherapy• Harnesses the patient's own immune system to

fight diverse cancer types (Bayer et al 2017)• Four major categories:

1. Monoclonal Antibodies2. Checkpoint Inhibitors3. Oncolytic Viral Therapy4. Chimeric Antigen Receptor T Cells

Timeline of Events in the development of Immun‐oncology

1950 1960 1970 1980 1990 2000 2010 2015

Autologous BMT

Allogeneic BMT

Donor Lymphocyte Infusions

INF‐α

Rituximab(Anti‐CD20)

mAb

Brentuximab Vedotin

(Anti‐CD30)mAb

Checkpoint InhibitorsIpilimumabNivolumab

Pembrolizumab

IL‐2

Tumor Infiltrating

LymphocytesCAR TTherapies

BCG mouse studies

William Coley 1890’s

TNFa

Link b/t HIV – Kaposi’s sarcoma

TVEC approved for adv melanoma

BCG approval for bladder cancer

Cancer immunosurveillance 1957

Ginex, et al., 2017


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Paradigm Shift in Oncology-Immunotherapy

How the Normal Immune System Functions

How the Normal Immune System Functions: Overview of B cells & T cells

B Cells

• B cell development• B cell function

T Cells

• T cell development• T cell function

NIH (2013); Murphy K. (2011) .


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Cell Mediated Immune Response

Molnar, C. & Gair, J. (2015). Concepts of Biology‐ 1st Canadian Edition. [E‐version]. Accessed 1/7/18 at https://opentextbc.ca/biology/chapter/12‐3‐adaptive‐immunity/. Licensed under Creative Commons Attribution 4.0 International License.

Three E’s of cancer immunoediting

Used with permission, Dunn et al., Nature, 2002

• Chemotherapy and AutoHCT

• Monoclonal Antibodieso Rituximab and

Herceptin

• Antibody-Drug Conjugates

o Brentuximab

• Tumor Checkpoint Blockade – PD-L1

New Approaches

Target the Tumor

• Vaccination

• Oncolytic viruses

• Immune Modulators

o Lenalidomide

• Immune Checkpoint Blockade

o PD1, CTLA4

Target the Host

• Allogeneic HCT

• Bispecific Antibodies

• Blinotumumab

• CAR T Therapy

• Oncolytic viruses

Target bothTumor + Host


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Immunotherapy • Four major categories:

1. Monoclonal Antibodies2. Checkpoint Inhibitors3. Oncolytic Viral Therapy4. Chimeric Antigen Receptor T Cells

Case Study

Case Study• 65 yo male- “Mike”• Presents with 10 pound weight loss, palpable L sided

cervical lymph nodes, and progressive fatigue. • CXR reveals mediastinal lymphadenopathy• Labs: Unremarkable, with exception of LDH in the 700’s• Bx of lymph node reveals DLBCL• Pt begins treatment with R-CHOP x 6 cycles


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Monoclonal Antibodies

Monoclonal Antibodies (MoAbs)• Substances that have the capability to act as a

naturally made antibody within the human body but are created to target a specific antigen.– Restore– Enhance– Mimic

Bayer, V., Amaya, B., Baniewicz, D., Callahan, C., Marsh, L., et al. (2017)

MoAbs by classAntibody/Agent Target Disease Side effect profile

Trastuzumab (Herceptin) HER2 HER2 positive Breast Cardiac toxicity, pulmonary toxicity, HTN, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea, acute infusion reactions

Bevacizumab (Avastin) VEGF CR, NSCL, Renal Cardiac toxicity, pulmonary toxicity, HTN, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea

Cetuximab (Erbitux) EGFR H&N, CR Cardiac toxicity, acute infusion reaction, pulmonarytoxicity, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea

Panitumumab (Vectibix) EGFR CR Cardiac toxicity, acute infusion reaction, pulmonarytoxicity, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea

Ipilimumab (Yervoy) CTLA‐4 Melanoma Enterocolitis, acute infusion reactions, endocrinopathies,diarrhea, fatigue

Rituximab (Rituxan) CD20 NHL, CLL CRS, tumor lysis syndrome, mucositis, nausea, fatigue, SOB, neutropenia

Adapted from Scott, A, Allison, J. & Wolchok, J., 2012,


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New MoAB Approvals in 2017Antibody/Agent Target Disease Side effect profile

obinutuzumab (Gazyva®) Hu CD20 Advanced FL acute infusion reactions, tumor lysis, cytopenias, hep B virus reactivation, PML

gemtuzumab ozogamicin(Mylotarg™)

CD33 AML acute infusion reactions, hepatotoxicity, hemorrhage, infection, QT prolongation

inotuzumab ozogamicin(Besponsa™)

CD 22 B‐cell ALL acute infusion reactions, hepatotoxicity, cytopenias, infection, fatigue, hemorrhage

Genentech, 2017; Pfizer Oncology, 2017.

Check Point Inhibitors

Checkpoint Inhibitors

Adapted from Mellman et al., Nature 2011, with permission

•Use the immune system to fight cancer by unleashing T‐cells to attack cancer cells

•Prevent tumor from blocking T‐cell activity


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Immune Checkpoints

• T cells have inhibitory and excitatory receptors– Excitatory turn ON the T cell (gas)– Inhibitory turn OFF the T cell (brake)

• Goal with immune checkpoint blockade is to BLOCK the inhibition of the T cell

• Release the brake, and allow the T cell to GO

Drug Name Indications

Anti‐CTLA4 Ipilimumab(YERVOY®) ‐Unresectable or metastatic melanoma

‐Adjuvant treatment melanoma

Anti‐PD1 Nivolumab

(OPDIVO®)

‐Unresectable or Metastatic Melanoma

‐Metastatic Non‐Small Cell Lung Cancer

‐ Renal Cell Carcinoma

‐Classical Hodgkin Lymphoma

‐Squamous Cell Carcinoma of the Head and Neck

‐Urothelial Carcinoma

Pembrilizumab

(KEYTRUDA®)

‐Melanoma

‐Non‐Small Cell Lung Cancer

‐Head and Neck Cancer

‐Classical Hodgkin Lymphoma

‐Urothelial Carcinoma

‐Microsatellite Instability‐High Cancer

Anti‐PDL1 Atezolizumab

(Tecentriq®)

‐Locally Advanced or Metastatic Urothelial Carcinoma

‐Metastatic Non‐Small Cell Lung Cancer

Avelumab

(BAVENCIO®)

‐Metastatic Merkel cell carcinoma (MCC)

‐Locally advanced or metastatic urothelial carcinoma

Durvalumab

(IMFINZI®)

‐Locally advanced or metastatic urothelial carcinoma

Bristol‐Meyers Squibb company 2017; Merck Sharp & Dphme Corp. 2017 ; EMD Serrano, 2017; Genentech, Inc. 2017; AztraZeneca 2017

Oncolytic Viruses


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Bayer et al., 2017

Oncolytic viral immunotherapy (OVI) is a viral targeted therapy that directly kills cancer cells by causing tumor death, producing tumor-toxic cytokines or antitumor host immune responses

Two ways viruses can be used in treatment:1. As the sole therapy2. As a vector for the delivery of the

therapy

Four mechanisms of action are related to OVIs: viral cell receptor response, cytokine release, nuclear replication, and extracellular immune response

Two types of OVIs are nonpathogenic (harmless to humans) and pathogenic (requiring genetic modification for use)

Oncolytic Viruses

Oncolytic VirusesExamples Indication

Talimogene lahaerparepvec (T-VEC) -Modified Herpes Simplex Virus 1 (IMLYGIC ®)

Advanced melanomas with injectable, unresectable tumor – cutaneous, subcutaneous, nodal lesions

Amgen, 2017

Case Study


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Case Study

• Mike’s lymphoma has progressed despite receiving R-CHOP x 6, salvage chemotherapy with RICE x3, and an Autologous HCT.

• He’s referred to a tertiary cancer center for consultation for CAR-T cells.

CAR T- Cells

Chimeric Antigen Receptor (CAR) T Cells

• A type of adoptive cell therapy• T-cells are genetically modified to express a chimeric

antigen receptor (CAR) that binds to target antigens displayed on the tumor

• When binding occurs, T-cells are activated, leading to T-cell proliferation and differentiation, secretion of cytokines, and direct cell kill

• May persist and lead to immunologic memory for antigen

Kalos, et al., 2011; Riddell, 2014


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CAR T cell manufacturing• T Cell Selection/Activation• Genetic modification (retroviral or lentiviral

vectors)• Expansion of T cells in culture• ± Cryopreservation

Zhang, et al., 2017

CAR T Cell Engineering

Image credit: Jackson, H.J., Rafiq, S., and Brentjens, R.J. (2016). Driving CAR T cells forward. Nature Reviews Clinical Oncology,13, 370–383. Used with permission.

Antigen Targets in Clinical TrialsTarget Disease

CD 19 Lymphoid malignancies

BCMA Multiple Myeloma

CD 20 NHL

CD 22 NHL

ROR1 CLL, MCL, ALL, TNBC, NSCLC

GD2 Glioblastoma; Neuroblastoma; Sarcoma

CEA Pancreatic CA; colorectal CA; hepatocellular CA

PSCA; PSMA‐TGFβRDN Prostate CA

EGFR Solid tumors

Mesothelin Solid tumors

HER2 Solid tumors

Retrieved on 1/28/18 from www.clinicaltrials.gov


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FDA Approved CAR T Cell Agents

Agent Target Indication

tisagenlecleucel(KYMRIAH™)

CD 19 2nd Relapse or refractory B‐cell ALL in pts up to age 25

Axicabtagene ciloleucel(YESCARTA™)

CD 19 Relapsed or refractory aggressive NHL (after 2 lines of therapy) in patients over age 18

Kite pharma, 2017; Novartis, 2017

CAR T Cell Therapy Logistics• Center Selection

– Clinical trials at select centers– Limited certified sites for FDA approved agents

• Relocation may be required– Requirements to stay near treating center during and after

therapy for monitoring• Assess caregiver requirements• Insurance clearance

CAR T Cell Treatment Overview

•Treatment eligibility & consenting

•Leukapheresis

•CAR T‐cell manufacturing

Pre Treatment

•Lymphodepletingchemo

•CAR T‐Cell Infusion

CAR T Cell Therapy •Toxicity monitoring

(intensively for 4 weeks post)

•Disease re‐staging

•Long term follow‐up

Post Treatment


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Models of Care for CAR T CellsInpatient Outpatient

• Most common approach• Hospitalization for cell infusion and

post infusion monitoring for 7 days• Discharge to OPD following therapy

after pre‐defined monitoring period or resolution of toxicities

• Ability to rapidly access trainedinpatient and emergency care

• Frequent visits post infusion• Close proximity to treating center (w/in

2hrs) post infusion • Patient & caregiver education (wallet

cards)

Kymriah™ REMS, 2017; Yescarta™ REMS, 2017

CAR T Cell Infusion• Lymphodepleting chemotherapy

– Fludarabine 30mg/m2 & Cyclophosphamide 300‐500 mg/m2 common– Chemo given to create immunological “space” to allow expansion of CAR T cells

• CAR T cell infusion – Generally 2 days after lymphodepletion– Cells are infused intravenously, usually over 30 minutes or faster by gravity– Premedicate w/ acetaminophen & diphenhydramine. – Cells defrosted for infusion, chain of custody verifications– Central lines recommended.– Acute infusion reactions may occur, though uncommon

Kalos & June, 2013; Novartis, 2017; Kite, 2017

Case Study


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Developing a Treatment Plan: Symptom & Toxicity Profiles

Determining severity: Grading irAE

• Common Terminology Criteria for Adverse Events (CTCAE):– Definition: An objective and consistent method for measuring

side effects.• Grading

1. Grade 1-Mild2. Grade 2- moderate 3. Grade 3-severe 4. Grade 4- life-threatening 5. Grade 5- fatality

CAR T Cells

Toxicities and Side Effects


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Cytokine Release Syndrome (CRS)

79% Tisagencleucel

94% AxicabtageneCiloleucel

(all grades)

Neurotoxicity

65% Tisagencleucel

87% AxicabtageneCiloleucel

(all grades)

On target, off tumortoxicities

Tumor Lysis

Syndrome

Infections

Common Toxicities of CAR T Cells

Image Credit: Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths. (2015). Killer T cells surround a cancer cell. National Institutes of Health. Licensed under a CC‐BY‐NC‐2.0 .

Brudno & Kochenderfer, 2016.; Kymriah™ REMS, 2017; Yescarta™ REMS, 2017

CRS Toxicities by Organ System

Image credit: Brudno, J. & Kochenderfer, J. (2016). Toxicities of chimeric antigen receptor T cells: Recognition and management. Blood, 127; 3321‐3330. Used with permission.

Cytokine Release SyndromeGrade Toxicity Management

Grade 1 Non‐life threatening (fever, nausea, etc) Supportive care Assess for/treat infectionAdmission generally indicated for fever

Grade 2 Moderate interventions required (ex: oxygen support, supportable hypotension, moderate organ toxicity)

Supportive care ICU may be indicated if pressorsConsider Tocilizumab 8mg/kg (max dose 800mg/dose), repeat dosing if needed± Corticosteroids for high‐risk patients

Grade 3 Aggressive interventions required (ex: O2 needs ≥ 40%, severe organ toxicity, severe hypotension)

Supportive careICU level care usually requiredTocilizumab 8mg/kg (max 800mg/dose), repeat if necessary± Corticosteroids (Dexamethasone 10mg IV q 6 hours or Methylprednisolone 1mg/kg q 12hrs)

Grade 4 Life‐threatening sx (ex: intubation, severe organ toxicity)

Supportive careICU level care requiredTocilizumab 8mg/kg (max 800mg/dose), repeat if necessary± Corticosteroids (Methylprednisolone 1gm daily)

Grade 5 Death

Adapted from Lee, D.W., et al. (2014); Kymriah™ REMS, 2017; Yescarta™ REMS, 2017


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Supportive Care: CRS• VS frequently

– Continuous pulse ox or telemetry may be warranted ≥ Grade 2• Frequent physical and neurological exams• Fever: R/O infection; anti-pyretics prn if febrile• Prophylactic abx and anti-virals• Follow labs & serum inflammatory markers

– Ex: CBC, CMP, Coags, CRP, Ferritin, IL-6• Monitor I/O, weights• Hypotension: Fluids to maintain MAP, vasopressors• Transfuse as needed for coagulopathies, anemia, thrombocytopenia• Neutropenia- GCSF used by some centers• Oxygen support as needed• Severe toxicities may require dialysis, mechanical ventilation

Brudno & Kochenderfer, 2016.; Kymriah™ REMS, 2017; Yescarta™ REMS, 2017

Neurotoxicity• Can occur w/ or w/o CRS, but

more often in conjunction with or after CRS onset

• Pathophysiology hypothesized to be due to endothelial activation and cytokines crossing the blood brain barrier.

• May be mild to severe– Headaches– Anxiety– Aphasia – Encephalopathy– Dizziness – Tremor– Seizures– Delirium– Cerebral edema

Turtle, et al., 2017; Gust, et al, 2017; Kymriah™ REMS, 2017; Yescarta™ REMS, 2017

Neurotoxicity Grading

Adapted from National Cancer Institute CTCAE Grading criteria v. 4.03, 2010.

CTCAE v4.0 Terms Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

SomnolenceMild but more than usual drowsiness or sleepiness

Moderate sedation; limiting instrumental ADL Obtundation or stupor

Life-threatening consequences; urgent intervention indicated Death

DizzinessMild unsteadiness or sensation of movement

Moderate unsteadiness or sensation of movement; limiting instrumental ADL

Severe unsteadiness or sensation of movement; limiting self care ADL - -

Tremor Mild symptomsModerate symptoms; limiting instrumental ADL

Severe symptoms; limiting self care ADL - -

Headache Mild painModerate pain; limiting instrumental ADL

Severe pain; limiting self care ADL - -

Encephalopathy Mild symptomsModerate symptoms; limiting instrumental ADL

Severe symptoms; limiting self care ADL

Life-threatening consequences; urgent intervention indicated Death

SeizureBrief partial seizure; no loss of consciousness Brief generalized seizure

Multiple seizures despitemedical intervention

Life-threatening; prolonged repetitive seizures Death

Edema cerebral - - -

Life-threatening consequences; urgent intervention indicated


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Neurotoxicity Management• Supportive care

– Sz precautions, anti-sz meds prophylactically– Aspiration precautions– Transfer to ICU for severe toxicities (ie: ICP monitoring)– R/O other etiologies of neurologic abnormalities (ex: MRI, CT, EEG, LP)

• If concurrent CRS, administer IL-6 Blockade (Tocilizumab)• Corticosteroids- Treat according to institutional algorithm or REMS

guidelines– For Grade 2 - 3: Dexamethasone 10mg IV q 12hrs to 6hrs– For Grade 4: Methylprednisolone 1 gm/daily x 3

Yescarta™ REMS, 2017; Neelapu, et al., 2017

Long-term Monitoring • Hypogammaglobulinemia with CD 19 CAR T• Disease restaging and monitoring for relapse• Long-term follow-up

– FDA- 15 year f/u for patients treated with replication-competent viral vectors

• Monitoring for secondary malignancies

FDA, 2016

Monoclonal Antibodies (MoAbs)



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MoAbs by classAntibody/Agent Target Disease Side effect profile

Trastuzumab (Herceptin) HER2 HER2 positive Breast Cardiac toxicity, pulmonary toxicity, HTN, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea, acute infusion reactions

Bevacizumab (Avastin) VEGF CR, NSCL, Renal Cardiac toxicity, pulmonary toxicity, HTN, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea

Cetuximab (Erbitux) EGFR H&N, CR Cardiac toxicity, acute infusion reaction, pulmonarytoxicity, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea

Panitumumab (Vectibix) EGFR CR Cardiac toxicity, acute infusion reaction, pulmonarytoxicity, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea

Ipilimumab (Yervoy) CTLA‐4 Melanoma Enterocolitis, acute infusion reactions, endocrinopathies,diarrhea, fatigue

Rituximab (Rituxan) CD20 NHL, CLL CRS, tumor lysis syndrome, mucositis, nausea, fatigue, SOB, neutropenia

(Scott, A, Allison, J. & Wolchok, J., 2012)

MoAbs: Side Effects• Hypersensitivity Reactions• Cardiac Toxicity• Pulmonary Toxicity• HTN• Diarrhea • Fatigue• Entrocolitis• Tumor Lysis• CRS

(Bayer, V., Amaya, B., Baniewicz, D., Callahan, C., Marsh, L., et al., 2017)

Checkpoint Inhibitors



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Based on the mechanism of action, there is potential for autoimmune activity in any organ system.

Immune-Related Adverse Effects (irAEs) include:

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Checkpoint Inhibitors: Side Effects & Toxicities

Colitis

HepatitisPneumonitis

Dermatitis

Immune-related Adverse Events (irAEs)\

pneumonitis

enteritis

colitisdermatitis

hepatitis

thyroiditis

hypophysitis uveitis

Pancreatitis/autoimmune diabetes

arthralgia/myalgia

myocarditissinusitis

Adrenal insufficiency

Basic irAE Management Principles

Ongoing surveillance

Identify appropriate intervention

events (CTCAE)Severity via common terminology criteria for adverse

events (CTCAE)

Determine cause (rule out non-inflammatory causes)

Assess signs and symptoms


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General Management by GradeGrade Management Follow up

Grade 1 Monitor patient closely Begin surveillancecalls/labs.

Grade 2 Delay of treatment

Initiate an oral corticosteroid (1mg/kg) for 4‐6 weeks

Continue surveillance; taper steroids slowly.

Grade 3/4 Higher corticosteroid dose (2mg/kg)

May require admission for IV steroids and/or IV hydration

Consider admission; post admission surveillance.

Adapted from CTCAE Grading criteria v. 4.03

Oncolytic Viral Therapy


Side Effects and ToxicitiesNeurologic Fatigue, chills, fever, headache, dizziness

Cardiac Vasculitis

Pulmonary Flu‐like symptoms, pneumonitis

Gastrointestinal Nausea, vomiting, diarrhea, constipation, abdominal pain, oral herpes

Renal Glomerulonephritis

Infectious Disease Herpes infections, systemic bacterial infection, cellulitis

Musculoskeletal Myalgias, arthralgias, pain in extremity

Dermatologic Necrosis, tumor tissue ulceration, impaired wound healing, and worsening psoriasis or vitiligo

Metabolic Weight loss

Miscellaneous Fever, pain at injection site

Amgen, 2017


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Side effects

• More than 25 % of patients experience– Fatigue, chills, fever, Flu-like symptoms, pain at injection site– Pyrexia, chills, and influenza-like illness can occur at any

time (more frequent first 3 months)– Cellulitis-most common grade 3 side event

• Premedication with acetaminophen

• TVEC is sensitive to acyclovir, in the event of herpetic infection

Amgen, 2017

Virus Precautions Protect against accidental spread. Perform adequate hygiene; cover area with a non permeable bandage

Avoid close contact with immunocompromised individuals

Precautions: pregnant women, children, immunocompromised individuals should avoid contact with the site/drug.

In treatment settings-contact isolation, staff education, PPE

Wall, L. & Baldwin‐Medsker, A. (2017)

Developing a Treatment Plan: Safe Handling and Administration


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Safe Handling and Administration

Lack of published evidence based guidance on the safe handling and administration of most

immunotherapy agents • ASCO/ONS chemotherapy administration

standards (Neuss, et al., 2016)

• Chemotherapy and Biotherapy Guidelines and Recommendations (Polovich, Olsen & LeFebvre., 2014).

• Education & Competencies

Wiley, K. et al., 2017

Developing a Treatment Plan: Financial Implications

Defining Financial Toxicity • High costs of cancer care, even in patients with

insurance, can lead to poorer outcomes, decrease quality of life, heighten stress and in some cases increase mortality rates

Chino et al., (2017).


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Statistics• 13% of nonelderly patients spend at least 20%

of their income on out-of-pocket expenses• 50% of Medicare beneficiaries pay at least 10%

of their income core treatment and out-of-pocket costs

Zafar, Y.S., 2015

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Financial Toxicity of Immunotherapies• Melanoma-

– Ipilumumab/Nivolumab $256,000 per year• Sarcoma –

– Ipilumumab/Nivolumab $46,704 per dose; $186, 816 total – Nivolumab $1830 per dose; total cost $47,580 per year

• Lymphoma (NHL)-– Axicabtagene Ciloleucel (YESCARTA™) $373,000 per dose– Brentuximab $294,000 per year

• GI-– Pembrolizumab $16,470 per dose; total cost $148,230

M. Lee Teh, personal communication. Jan. 5, 2018; Babashov, V. et al., 2017; ICER, 2017.

Financial Toxicity- CAR T Cells

• Complex and rapidly evolving insurance authorization processes

• Many payers still defining medical policy and approaches to coverage

• Intensive institutional financial coordination needed at time of referral to certified center


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Financial Toxicity’s Implications on Care

• Compliance • Oral regimens• Lower quality of life (Fenn, et al., 2017)

Preventing Financial Toxicity and the Future

• Transparency • Screen• Document • Offer resources• Advocate • ONS Tool Kit https://www.ons.org/sites/default/files/ONS_ONN_Toolkit_Financial_Issues_050417.pdf

Pirschel, C., 2017

Financial Assistance Programs• Cancer Financial Assistance Coalition• Cancercare Financial Assistance Program • HealthWell Foundation• Leukemia and Lymphoma Society • American Cancer Society

Expanded Access (Compassionate Use). FDA.gov. Jan. 20, 2018.


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Financial Assistance Programs- RX

• Compassionate Use • Patient Free Supply• Co-pay Assistance

Expanded Access (Compassionate Use). FDA.gov. Jan. 20, 2018.

Case Study: Financial Toxicity

Developing a Treatment Plan: Patient and Caregiver

Considerations


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Patient and Caregiver Considerations: Education

• Education– Multimodality treatments/ combination therapy – Response to immunotherapy compared to

traditional therapies– Toxicities differ from Chemotherapy – Early side effect recognition and open

communication with staff

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Patient and Caregiver Considerations: Education & Toxicity Management

• Should be pertinent to the type of Immunotherapy

• Safety Oriented• Encouraged to report

symptoms promptly• Evidence based & patient &

family centered

Patient

Drug‐specific

Evidence Based

Communication

Safety

CAR T Cell Patient Education Needs• Central line• Birth control precautions• Wallet card• Refrain from driving and hazardous occupations

for 8 weeks post treatment• Proximity to center & f/u visit requirements after

treatment

Novartis, 2017; Kite, 2017 Photo courtesy of Seattle Cancer Care Alliance. Used w/ permission


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Patient and Caregiver Considerations• Coordination

– Access• Multi Center Coordination

– Treatment schedules– Infection control considerations– Access to emergent care in case of

toxicity– Clinical Trials

• Psychosocial– Anxiety r/t efficacy and the “unknown”– Stress R/T diagnosis, disease

progression, hospitalizations, deterioration in quality of life

– Impact on QOL

Patient and Caregiver Considerations: Survivorship & Long Term Follow up

• Late Effects • Palliative Care• ONS Research Agenda

Patient and Caregiver Considerations: The Nurse’s Role

• Educator• Coordinator of care• Chairside/bedside

– Assessment– Administration– Understanding both of IO

agents AND toxicity management

• Patient/caregiver support and advocateMultidisciplinary approach


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Development of a Treatment Plan: Implications of IO on Nursing &

the Future

Implications of IO for Nursing Practice

• Urgent need to educate nurses to empower and ensure evidence based delivery of care.

• Opportunity to contribute to the development of evidence to ensure the delivery of patient centered care.

Implications of IO for Nursing Practice: The Future

• Research on symptom management & quality of life

• Patient reported outcomes (PROs)– Clinician vs Patient perspective

• Late effects of immunotherapy• Survivorship


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Acknowledgements

Special Thanks To:• Seattle Cancer Care Alliance leadership and

staff• Bezos Family Immunotherapy Clinic Staff• University of Washington BMT & Heme-Onc

Platinum services• Fred Hutch program in Immunology• Kathleen Shannon-Dorcy, PhD, RN, SCCA

Director of Clinical/Nursing Research, Education and Practice

• Drs. David Maloney, Cameron Turtle, and Stan Riddell

Contact:

Karen [email protected]

Acknowledgements

Special Thanks To:• Mimma Errante, MS NP-C OCN Clinical

Trials NP• Ruth-Ann Gordon, MSN FNP-BC OCN

Clinical Trials Nurse Coordinator, MSKCC• Memorial Sloan Kettering Cancer Center

Department of Nursing

Contact:Abi [email protected]

Questions


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References• Amgen (2017). Talimogene lahaerparepvec (T-VEC). [Package insert]. Retrieved from

http://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/imlygic/imlygic_pi.pdf• AztraZeneca (2017). Imfinzi™(durvalumab) [Package insert]. Retrieved from

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761069s000lbl.pdf• Babashov, V., Begen, M.A., Mangel, J., Zaric, G.S. (2017). Economic evaluation of brentuximab vedotin for

persistent Hodgkin's lymphoma. Current Oncology, 24(1), e6–e14.• Bayer, V., Amaya, B., Baniewicz, D., Callahan, C., Marsh, L., & McCoy, A. S. (2017). Cancer immunotherapy:

An evidence-based overview and implications for practice. Clinical Journal of Oncology Nursing, 21(2), 13-21. • Bristol-Myers Squibb. (2011). Yervoy™ (ipilimumab) [US package insert]. Retrieved from

https://packageinserts.bms.com/pi/pi_yervoy.pdf• Brudno, J., & Kochenderfer, J. (2016). Toxicities of chimeric antigen receptor T cells: Recognition and

management. Blood : Journal of the American Society of Hematology., 127(26), 3321-3330.

References• Chino, F., Pepercorn, J.M., Rushing, C., Kamal, A.H., Alotmare, I., Samsa, G., & Zafar, S. Y. (2017)

Out-of pocket costs, financial distress and underinsurance in cancer care. JAMA Oncology, 3(11), 1582-1584.

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