Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B‐Lineage ALL Sue Zupanec, MN, NP Susie Burke, MA, CPNP, CPHON ® COG Educational Track at APHON 2018 1 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 1 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Disclosure ▪ Sue Zupanec and Susie Burke have no industry relationships. ▪ Off label use will be discussed. 2 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 2 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM COG Disclosure The information in this presentation is intended for educational purposes only and is solely for the use of the individual nurse learner. This information is not intended as the sole source of guidance in providing Children’s Oncology Group (COG) protocol-directed nursing care, and current COG protocols should always be consulted prior to making patient care decisions for any patient enrolled on a COG protocol. Learners should also be aware that COG protocols are research plans designed to investigate particular study questions, that recommendations for treatment and dosing are made within the context of specific research aims, and that these recommendations are intended only for use within a structured research setting. Although every attempt has been made to assure that the informational content contained herein is as accurate and complete as possible as of the date of presentation, no warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of this content. This information may not be copied or redistributed in any form, or used for any purpose other than nursing education. 3 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 3 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Learning Objectives Learning Outcomes At the completion of this presentation, the participant will be able to: . Describe general toxicities for MoABs, and the more unique toxicities related to Blinatumomab and Inotuzumab . Compare and contrast current COG treatment options for patients with B-lineage ALL in 1st and 2nd relapse . Consider important components when developing a nursing care plan for patients receiving Blinatumomab and Inotuzumab 4 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 4 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Background of the Problem . Despite highly effective front-line therapies for ALL, there continues to be a subset of patients who remain at increased risk of relapse or who have refractory disease . Current standard regimens for relapsed ALL employ intensive cytotoxic therapy with potential for significant short and long-term toxicities ♦ Further dose escalation of therapy is unlikely to improve outcomes and may result in increased toxicities . Novel therapeutic strategies are needed to reduce the rate of secondary complications, relapses and refractory subtypes 5 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 5 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM ALL Relapse Rates by Risk Category COG patients with B- or T-ALL from 1988-2002: 1961/9585 (20.5%) experienced a relapse 80% 78% 68% 60% 59% 60% 44% 44% 40% 39% 40% 24% 18% 20% 12% 12% 0% Early Intermediate Late Overall Isolated Marrow Combined Isolated CNS Data from Nguyen et al. (2008) 6 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 6 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Cancer Immunotherapy . Broad category of cancer therapies that ♦ Work to harness the innate powers of the immune system ♦ Fight cancer by recognizing and attacking CHEMO SURGERY cancer cells ♦ Seek to make cancer cells more obvious to the immune system . Often used in conjunction with other cancer treatments IMMUNE XRT THERAPY 7 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 7 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Components of the Immune System 8 Illustrations by Alice Yang, 2011 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 8 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Innate and Adaptive Immunity Innate Immunity Adaptive Immunity (Rapid Response) (Slow Response) 9 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 9 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM What are Cell Surface Antigens? . Proteins expressed on the surface of cells . Serve as markers for specific cell types such as B or T lymphocytes . Responsible for specific biologic processes 10 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 10 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Immunotherapy: A Targeted Approach . Targeted therapy (AKA precision therapy) ♦ Refers to a new generation of cancer drugs designed to interfere with specific molecules involved in tumor growth and progression ♦ Has significantly altered the approach to treatment of all types of cancers, including leukemia . Utilization of well-planned clinical trials ♦ Requires exceptional nursing care to ensure that these complicated agents are administered in a safe and timely manner to our patients ♦ Offers hope for the future 11 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 11 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Immunotherapy: How Does It Work Prevent, block, or Make cancer interrupt cell cells more growth receptive to . Some agents have immune Cut off blood ♦ system flow to tumor The ability to accomplish more than (antiangiogenesis) one method of action ♦ Unique and specific actions against TARGETED the cancer cell THERAPIES Cause cell Target death defects in (apoptosis) the cancer cells Carry other drugs to a tumor 12 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 12 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Properties of Immunotherapy Powerful Specific Memory Universal 13 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 13 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Types of Immunotherapy . Monoclonal Antibodies . Immune Checkpoint Inhibitors . Non-specific Immunotherapies . Cancer Treatment Vaccines . T-cell Therapy ♦ Chimeric Antigen Receptor (CAR) T-cell therapy 14 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 14 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Types/Nomenclature of Monoclonal Antibodies Murine Chimeric Humanized Fully Human (0% human) (65% human) (>90% human) (100% human) -0mab -ximab -zumab -umab High Potential for immunogenicity Low 15 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 15 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM CRS (cont.) . Risk factors ♦ First infusion • Usually within the first 2 hours of infusion ♦ High tumor burden ♦ No prior chemotherapy . Prevention ♦ Use of pre-meds-Tylenol/Benadryl ♦ Some pts also require Dexamethasone . Treatment ♦ Tocilizumab is initiated with severe CRS 16 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 16 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM CRS Toxicity Grading System Grade Clinical Picture Management 1 Mild: Flu-like symptoms, fever, myalgia •Antipyretics •Supportive care 2 Moderate: beginning S/S of organ dysfunction (e.g. grade 2 creatinine, •Hospitalization grade 3 LFTs) •IV therapies 3 Severe: ↑ing S/S of organ dysfunction •O2/IVFs/pressors (e.g. grade 3 creatinine, grade 4 LFTs), hypotension, coagulopathy, hypoxia •FFP/Cryo •Anti IL-6-Tocilizumab 4 Life threatening: Significant hypotension/ Hypoxia •Multiple pressors •Ventilator support •Anti IL-6-Tocilizumab Porter, D. ASH, December 14, 2014 17 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 17 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Other Common Toxicities Associated with MABs General • Hypersensitivity GI • Nausea • Allergic reaction Skin • Rash/Pruritis •Neuro • Peripheral neuropathy • Impaired wound healing • Seizures Flu-like syndrome • HA Immune mediated • Hepatitis • Fever • Nephritis • Fatigue • Pneumonitis • Impaired thyroid function Pulmonary • Capillary leak syndrome Miscellaneous • Serious bleeding • Thrombosis Renal • TLS • Proteinuria • Hypertension • Electrolyte abnormalities 18 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 18 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM Meet Kayla Initial Dx: 10/2015 Presentation: WBC 85x109/L, CNS1, Neutral cytogenetics, BMA confirmed pre-B-lineage ALL, EOI MRD- neg PMH: ASD, no other health issues Social Hx: Lives 2 hrs from treatment center with biological parents 3 siblings ages 18 mos, 2 & 5 yrs Family income <50K/yr Treatment: HR Protocol AALL0232 19 C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 19 Thursday,