Immuno-Oncology: How to Develop a Treatment Plan

Transcription

1 Immuno-Oncology: How to Develop a Treatment Plan Wednesday, May 16 3:30 5:30 pm Note one action you ll take after attending this session: Karen Anderson, MN, RN, AOCNS, BMTCN, CRNI Clinical Operations Manager Bezos Family Immunotherapy Clinic Seattle Cancer Care Alliance kcanders@seattlecca.org Abigail Baldwin-Medsker, MSN, RN, OCN Memorial Sloan Kettering Cancer Center baldwina@mskcc.org Key Session Takeaways 1. Learner will identify potential treatment plan options for patients receiving immune-oncology. 2. Learner will identify two potential toxicities of CAR T-cell therapy and management strategies. 3. Learner will describe nursing considerations for a patient with financial toxicity. Preconference Oncology Nursing Society 43nd Annual Congress May 17 20, 2018 Washington, DC 1

2 ONS Pre Conference Immuno-Oncology: How To Develop a Treatment Plan Karen Anderson MN, RN, AOCNS, BMTCN, CRNI Abigail Baldwin-Medsker MSN, RN, OCN Disclosures No disclosures Preconference 1

3 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 Preconference 2

4 Immunotherapy Harnesses the patient's own immune system to fight diverse cancer types (Bayer et al 2017) Four major categories: 1. Monoclonal Antibodies 2. Checkpoint Inhibitors 3. Oncolytic Viral Therapy 4. Chimeric Antigen Receptor T Cells Timeline of Events in the development of Immun oncology William Coley 1890 s BCG mouse studies TNFa BCG approval for bladder cancer TVEC approved for adv melanoma Cancer immunosur veillance 1957 Autologous BMT Allogeneic BMT Donor Lymphocyte Infusions Tumor Infiltrating Lymphocytes Rituximab (Anti CD20) mab Brentuximab Vedotin (Anti CD30) mab INF α IL Ginex, et al., 2017 Link b/t HIV Kaposi s sarcoma CAR T Therapies Checkpoint Inhibitors Ipilimumab Nivolumab Pembrolizumab Preconference 3

5 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). Preconference 4

6 Cell Mediated Immune Response Molnar, C. & Gair, J. (2015). Concepts of Biology 1 st Canadian Edition. [E version]. Accessed 1/7/18 at 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 New Approaches Target the Tumor Chemotherapy and AutoHCT Monoclonal Antibodies o Rituximab and Herceptin Antibody-Drug Conjugates o Brentuximab Tumor Checkpoint Blockade PD-L1 Target the Host Vaccination Oncolytic viruses Immune Modulators o Lenalidomide Immune Checkpoint Blockade o PD1, CTLA4 Target both Tumor + Host Allogeneic HCT Bispecific Antibodies Blinotumumab CAR T Therapy Oncolytic viruses Preconference 5

7 Immunotherapy Four major categories: 1. Monoclonal Antibodies 2. Checkpoint Inhibitors 3. Oncolytic Viral Therapy 4. 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 Preconference 6

8 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 class Antibody/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, pulmonary toxicity, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea Panitumumab (Vectibix) EGFR CR Cardiac toxicity, acute infusion reaction, pulmonary toxicity, 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, Preconference 7

9 New MoAB Approvals in 2017 Antibody/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 ) inotuzumab ozogamicin (Besponsa ) CD33 AML acute infusion reactions, hepatotoxicity, hemorrhage, infection, QT prolongation CD 22 B cell ALL acute infusion reactions, hepatotoxicity, cytopenias, infection, fatigue, hemorrhage Genentech, 2017; Pfizer Oncology, Check Point Inhibitors Checkpoint Inhibitors Use the immune system to fight cancer by unleashing T cells to attack cancer cells Prevent tumor from blocking T cell activity Adapted from Mellman et al., Nature 2011, with permission Preconference 8

10 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 Unresectable or Metastatic Melanoma (OPDIVO ) Metastatic Non Small Cell Lung Cancer Renal Cell Carcinoma Classical Hodgkin Lymphoma Squamous Cell Carcinoma of the Head and Neck Urothelial Carcinoma Pembrilizumab Melanoma (KEYTRUDA ) Non Small Cell Lung Cancer Head and Neck Cancer Classical Hodgkin Lymphoma Urothelial Carcinoma Microsatellite Instability High Cancer Anti PDL1 Atezolizumab Locally Advanced or Metastatic Urothelial Carcinoma (Tecentriq ) Metastatic Non Small Cell Lung Cancer Avelumab Metastatic Merkel cell carcinoma (MCC) (BAVENCIO ) Locally advanced or metastatic urothelial carcinoma Durvalumab Locally advanced or metastatic urothelial carcinoma (IMFINZI ) Bristol Meyers Squibb company 2017; Merck Sharp & Dphme Corp ; EMD Serrano, 2017; Genentech, Inc. 2017; AztraZeneca 2017 Oncolytic Viruses Preconference 9

11 Oncolytic Viruses Oncolytic viral immunotherapy (OVI) is a viral targeted therapy that directly kills Four mechanisms of action are related cancer cells by causing tumor death, to OVIs: viral cell receptor response, producing tumor-toxic cytokines or cytokine release, nuclear replication, antitumor host immune responses and extracellular immune response Two ways viruses can be used in treatment: 1. As the sole therapy 2. As a vector for the delivery of the therapy Two types of OVIs are nonpathogenic (harmless to humans) and pathogenic (requiring genetic modification for use) Bayer et al., 2017 Oncolytic Viruses Examples Talimogene lahaerparepvec (T- VEC) -Modified Herpes Simplex Virus 1 (IMLYGIC ) Indication Advanced melanomas with injectable, unresectable tumor cutaneous, subcutaneous, nodal lesions Amgen, 2017 Case Study Preconference 10

12 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 Preconference 11

13 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, Used with permission. Antigen Targets in Clinical Trials Target 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 Preconference 12

14 FDA Approved CAR T Cell Agents Agent Target Indication tisagenlecleucel CD 19 2 nd Relapse or refractory B cell ALL in (KYMRIAH ) 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 CAR T Cell Therapy Lymphodepleting chemo CAR T Cell Infusion Toxicity monitoring (intensively for 4 weeks post) Disease re staging Long term follow up Post Treatment Preconference 13

15 Models of Care for CAR T Cells Inpatient 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 Outpatient Ability to rapidly access trained inpatient 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 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 Preconference 14

16 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-Mild 2. Grade 2- moderate 3. Grade 3-severe 4. Grade 4- life-threatening 5. Grade 5- fatality CAR T Cells Toxicities and Side Effects Preconference 15

17 Common Toxicities of CAR T Cells Neurotoxicity 65% Tisagencleucel 87% Axicabtagene Ciloleucel (all grades) Infections Tumor Lysis Syndrome On target, off tumor toxicities Cytokine Release Syndrome (CRS) 79% Tisagencleucel 94% Axicabtagene Ciloleucel (all grades) 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; Used with permission. Cytokine Release Syndrome Grade Toxicity Management Grade 1 Non life threatening (fever, nausea, etc) Supportive care Assess for/treat infection Admission generally indicated for fever Grade 2 Moderate interventions required (ex: oxygen support, supportable hypotension, moderate organ toxicity) Supportive care ICU may be indicated if pressors Consider Tocilizumab 8mg/kg (max dose 800mg/dose), repeat dosing if needed ± Corticosteroids for high risk patients Grade 3 Grade 4 Grade 5 Aggressive interventions required (ex: O2 needs 40%, severe organ toxicity, severe hypotension) Life threatening sx (ex: intubation, severe organ toxicity) Death Supportive care ICU level care usually required Tocilizumab 8mg/kg (max 800mg/dose), repeat if necessary ± Corticosteroids (Dexamethasone 10mg IV q 6 hours or Methylprednisolone 1mg/kg q 12hrs) Supportive care ICU level care required Tocilizumab 8mg/kg (max 800mg/dose), repeat if necessary ± Corticosteroids (Methylprednisolone 1gm daily) Adapted from Lee, D.W., et al. (2014); Kymriah REMS, 2017; Yescarta REMS, 2017 Preconference 16

18 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 CTCAE v4.0 Terms Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Somnolence Mild but more than usual drowsiness or sleepiness Moderate sedation; limiting instrumental ADL Obtundation or stupor Life-threatening consequences; urgent intervention indicated Death Dizziness Mild 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 symptoms Moderate symptoms; limiting Severe symptoms; limiting instrumental ADL self care ADL - - Headache Mild pain Moderate pain; limiting instrumental ADL Severe pain; limiting self care ADL - - Encephalopathy Seizure Mild symptoms Brief partial seizure; no loss of consciousness Life-threatening Moderate symptoms; limiting Severe symptoms; limiting consequences; urgent instrumental ADL self care ADL intervention indicated Life-threatening; Multiple seizures despite prolonged repetitive Brief generalized seizure medical intervention seizures Death Death Edema cerebral Adapted from National Cancer Institute CTCAE Grading criteria v. 4.03, Life-threatening consequences; urgent intervention indicated Preconference 17

19 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 Preconference 18

20 MoAbs by class Antibody/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, pulmonary toxicity, thromboembolus, neutropenia, fatigue, skin reactions, diarrhea Panitumumab (Vectibix) EGFR CR Cardiac toxicity, acute infusion reaction, pulmonary toxicity, 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 Preconference 19

21 Checkpoint Inhibitors: Side Effects & Toxicities Based on the mechanism of action, there is potential for autoimmune activity in any organ system. Immune-Related Adverse Effects (iraes) include: Dermatitis Colitis Pneumonitis Hepatitis 6 3 Immune-related Adverse Events (iraes) hypophysitis pneumonitis sinusitis enteritis colitis Pancreatitis/ autoimmune diabetes \ Adrenal insufficiency uveitis thyroiditis myocarditis hepatitis dermatitis arthralgia/ myalgia Basic irae Management Principles Assess signs and symptoms Determine cause (rule out non-inflammatory causes) Severity via common terminology criteria for adverse events (CTCAE) Identify appropriate intervention Ongoing surveillance Preconference 20

22 General Management by Grade Grade Management Follow up Grade 1 Monitor patient closely Begin surveillance calls/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 Oncolytic Viral Therapy Toxicities and Side Effects Side Effects and Toxicities Neurologic Fatigue, chills, fever, headache, dizziness Cardiac Pulmonary Gastrointestinal Renal Infectious Disease Musculoskeletal Dermatologic Metabolic Miscellaneous Vasculitis Flu like symptoms, pneumonitis Nausea, vomiting, diarrhea, constipation, abdominal pain, oral herpes Glomerulonephritis Herpes infections, systemic bacterial infection, cellulitis Myalgias, arthralgias, pain in extremity Necrosis, tumor tissue ulceration, impaired wound healing, and worsening psoriasis or vitiligo Weight loss Fever, pain at injection site Amgen, 2017 Preconference 21

23 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 Precautions: pregnant women, children, immunocompromised individuals should avoid contact with the site/drug. Avoid close contact with immunocompromised individuals In treatment settingscontact isolation, staff education, PPE Wall, L. & Baldwin Medsker, A. (2017) Developing a Treatment Plan: Safe Handling and Administration Preconference 22

24 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). Preconference 23

25 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-ofpocket costs Zafar, Y.S., 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, 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 Preconference 24

26 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 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, Preconference 25

27 Financial Assistance Programs- RX Compassionate Use Patient Free Supply Co-pay Assistance Expanded Access (Compassionate Use). FDA.gov. Jan. 20, Case Study: Financial Toxicity Developing a Treatment Plan: Patient and Caregiver Considerations Preconference 26

28 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 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 Safety Drug specific Patient Evidence Based Communication 85 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 Preconference 27

29 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 advocate Multidisciplinary approach Preconference 28

30 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 Preconference 29

31 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 Anderson 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 Baldwin-Medsker Questions Preconference 30

32 References Amgen (2017). Talimogene lahaerparepvec (T-VEC). [Package insert]. Retrieved from AztraZeneca (2017). Imfinzi (durvalumab) [Package insert]. Retrieved from 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), Bristol-Myers Squibb. (2011). Yervoy (ipilimumab) [US package insert]. Retrieved from 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), 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), Dunn, GP; Bruce, AT; Ikeda, H; Old, LJ; & Schreiber, RD. (2002). Cancer immunoediting: From immunosurveillance to tumor escape. Nature Immunology, 3, EMD Serano, Inc. (2017). Bavencio (avelumab). [Package insert]. Retrieved 1/28/18 from Expanded Access (Compassionate Use). U.S Food & Drug Administration. [FDA.gov.] Retrieved 1/20/2018 from m Fenn, K., Evans, S., McCorkle, R., DiGiovanna, M.P., Pusztai, L., Sanft, T., Chagpar, A. B. (2014). Impact of financial burden of cancer on survivors quality of life. Journal of Oncology Practice, 10(5), References Food and Drug Administration. (2006). Guidance for Industry: Gene therapy clinical trials- Observing subjects for delayed adverse events. Retrieved 1/28/18 from ularandgenetherapy/ucm pdf. Genentech, Inc. (2017). Tecentriq (atezolizumab) [Package insert]. Retrieved from Genentech, Inc. (2017). Gazyva (obinutuzumab). [Package insert]. Retrieved 1/28/18 from Ginex, P., Brassil, K., & Ely, B. (2017). Immunotherapy: Exploring the state of the science. Clinical Journal of Oncology Nursing, 21(2), Gust, J., Hay, K.A., Hanafi, L-A., Li, D. Myerson, D. and Turtle, C. (2017). Endothelial activation and blood brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discovery, 7 (12), Institute of Clinical and Economic Review (ICER). (2017). Chimeric antigen receptor T-cell therapy for B cell cancers: Effectiveness and value (Draft evidence review). Retrieved 1/28/18 from Preconference 31

33 References Kalos, M., Levine, B. L., Porter, D. L., Katz, S., Grupp, S. A., Bagg, A., & June, C. H. (2011). T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Science Translational Medicine, 3(95), 95ra73. Kalos, M., & June, C. H. (2013). Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity, 39(1), 10. Kite Pharma (2017). Yescarta (axicabtagene ciloleucel) [Package insert]. Retrieved 1/28/18 from Kite Pharma (2017). Yescarta (axicabtagene ciloleucel) Risk Evaluation and Mitigation Strategy. Retrieved 1/28/18 at Lee, D.W., Gardner, R., Porter, D.L., Louis, C. U., Ahmed, N., Jensen, M., Mackall, C.L. (2014). Current concepts in the diagnosis & management of cytokine release syndrome. Blood, 124(2), Mellman, I; Coukos, G; & Dranoff, G. (2011). Cancer immunotherapy comes of age. Nature, 480(7378), Merck Sharp & Dohme Corp. (2016). Keytruda (pembrolizumab) [Package insert]. Retrieved from References M. Lee Tee. [Personal Communication]. Jan. 5, Molnar, C. & Gair, J. (2015). Concepts of Biology- 1 st Canadian Edition. [E-version]. Accessed 1/7/18 at Murphy, K. (2011). Janesway Immunology. Garland Science. Eight edition. National Cancer Institute. (2010). Common Terminology Criteria for Adverse Events v4.03. NIH publication # Retrieved 1/28/18 from 14_QuickReference_5x7.pdf Neelapu, S., Tummala, S., Kebriaei, P., Wierda, W., Gutierrez, C., Locke, F.,... Shpall, E. (2017). Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nature Reviews., 15(1), Neuss, M. N., Gilmore, T. R., Belderson, K.M., Billett, A. L., Conti-Kalchik, T., Harvey, B.E., Polovich, M. (2016) Updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards, including standards for pediatric oncology. Journal of Oncology Practice, 12(12), Novartis. (2017). Kymriah (tisagenlecleucel). [Package insert]. Retrieved 1/28/18 from References Novartis. (2017). Kymriah (tisagenlecleucel). Risk evaluation and mitigation strategy. Retrieved 1/28/18 from Pirschel, C. (2017). Financial toxicity and its burden on cancer care. ONS Voice. 32(11), Pfizer Oncology. (2017). Besponsa (inotuzumab ozogamicin) [Package insert]. Retrieved 1/28/18 from Pfizer Oncology. (2017). Mylotarg (gemtuzumab ozogamicin) [Package insert]. Retrieved 1/28/18 from Polovich, Olsen & LeFebvre. (2014). Chemotherapy Biotherapy Guidelines and Recommendations for Practice: 4 th edition. Oncology Nursing Society. Riddell, S.R., Sommermeyer, D., Berger, C., Liu, L.S., Balakrishnan, A., Salter, A., Turtle, C.J. (2014). Adoptive therapy with chimeric antigen receptor-modified T cells of defined subset composition. The Cancer Journal, 20(2), Preconference 32

34 References Scott, A, Allison, J. & Wolchok, J. (2012). Monoclonal antibodies in cancer therapy. Cancer Immunity,12, 14. Turtle, C. J, Hay, K. A., Gust, J., Hanafi, L-A., Li, D., Liles, W.C., Maloney, D. G. (2017). Cytokine release syndrome (CRS) and neurotoxicity (NT) after CD19-specific chimeric antigen receptor- (CAR-) modified T cells. Journal of Clinical Oncology, 35(15), suppl; Understanding the immune system: How it works. (2003). US Department of Health and Human Services National Institute of Health. NO Wall, L. and Baldwin-Medkser, A. (2017) Safe and effective standard of care. Clinical Journal of Oncology Nursing, 21(5), E1-E7. Wiley, K., LeFebvre, K. Wall, L., Baldwin-Medkser, A., Nguyen, K., Marsh, L., and Baniewicz, D. (2017). Immunotherapy administration. Clinical Journal of Oncology Nursing, S21(2), 5-6. Zafar, S. Y. (2016). Financial toxicity of cancer care: Its time to intervene. Journal of the National Cancer Institute, 108(5), djv370. Zhang, C., Liu, J., Zhong, J. F., & Zhang, X. (2017). Engineering CAR-T cells. Biomarker Research, 5, 22. Preconference 33