immuno-oncology: how to develop a treatment plan · 1. learner will identify potential treatment...
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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: ____________________________________________________
________________________________________________________________________________
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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)
Toxicities and Side Effects
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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
Toxicities and Side Effects
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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
Toxicities and Side Effects
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
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