A Tale of Two Moabs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B‐Lineage ALL

Home , Blinatumomab, Inotuzumab ozogamicin

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

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.

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.

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

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

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

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)

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

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

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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

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

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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

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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

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

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

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 19 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

COG Trials for Relapsed B-Lineage ALL

AALL1331 – Blinatumomab with Relapsed ALL Therapy AALL1621 – Single Agent Inotuzumab Goals: 1. Overcome resistance 2. Minimize toxicity 3. Improve survival

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 20 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Kayla

Relapse #1: 11/2016 Presentation: Routine CBC showed peripheral blasts BMA/Bx: Confirmed relapsed pre-B-lineage ALL LP: CNS negative Diagnosis: Early isolated bone marrow relapse Protocol: Eligible for AALL1331 COG trial for 1st relapse Primary Aim: Will addition of blina to UKALLR3 backbone improve DFS for pediatric patients in 1st relapse of B-lineage ALL?

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 21 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Blinatumomab Any T Cell Mechanism of Action (BiTE = Bi-specific T-Cell Engager)

CD3

TCR Acts independently of specificity of TCR Blina- tumomab

Allows T cells recognition of TAA CD19 Does not require MHC Class I and/or peptide antigen

Tumor Cell

Slide courtesy of Dr. Lia Gore 22

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 22 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Blina – High Impact Paper: Pediatric Experience Phase 1 • Dose Finding: n=49 pediatric patients with relapsed/refractory B ALL • Established recommended dose for phase 2 Phase 2 Recommended dose • 5 mcg/m2 for 7 days then escalation to 15 mcg/m2 for days 8-28 Efficacy • n=44 patients (analysis on 70 patients treated at recommended dose) CR rate post 2 cycles • 27/70 patients (39%) • 14/27 (52%) also MRD negative CRS Grade 3 • 3/70 (4%) – steroid pre-treatment CRS Grade 4 • 1/70 (1%) – steroid pre-treatment Neurotoxicity Grade 2 • (seizure) 2/70 (3%) Pyrexia: • 80%

von Stackelberg, A et al. (2016), Journal of Clinical Oncology, 34, 1-11 23 Clinical trial information: NCT01471782. DOI: 10.1200/JCO.2016.67.3301

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 23 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Inotuzumab – InO

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 24 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Kayla

Relapse #2: 03/2017 Presentation: Routine BMA/Bx prior to pre-SCT evaluation showed relapse BMA/Bx: Change noted in immunophenotype of Kayla’s ALL CD19 no longer expressed on lymphoblasts, now has expression of CD22 (potential target) Outcome: Taken off AALL1331 Options/ CART-22 study – Phase I (not an open COG trial) Discussions: COG AALL1621 – Phase II – Inotuzomab open Supportive care/hospice

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 25 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

InO – High Impact Paper: Adult Experience

Phase 3 – Adults with Relapsed Refractory ALL N=218 (109 in each group) randomized to InO or Standard Arm Standard Arm InO Arm CR Rate: 24.9% CR Rate: 80.7% CR with MRD negative response: 28.1% CR with MRD negative response: 78.4% (MRD <0.01%) (MRD <0.01%) VOD: 1 patient (1%) VOD: 15 patients (11%) Remission Rates for Adult Patients with Relapsed/Refractory ALL receiving salvage therapy: • First attempt - 31-44% • Second attempt - 18-25%

INO-VATE ALL ClinicalTrials.gov number, NCT01564784 Kantarjian, H. et al. (2016) The New England Journal of Medicine, 375, 740-753 26

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 26 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

InO: Pediatric Experience

Compassionate Use in Pediatric Patients N=34 patients (age range 2.3-21.4 years) N=13 with previous HSCT N=27 previous CD19 directed treatment (Blina or CD19 CARTs) • 62% achieved CR • 13/18 with CR also achieved MRD negative remissions (MRD <0.01%) Infections: 38% had Grade 3/4 Hepatic Toxicity: Grade 1-4 Elevated Transaminases 11/34 (32%) No VOD/SOS during InO cycles 8/15 patients proceeded to HSCT post InO – 1 patient died from VOD/SOS

Bhojwani, D. (2017) Abstract 10512, Journal of Clinical Oncology 27 ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.10512

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 27 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

FDA Approval

. September 1, 2016 : FDA approval of Blinatumomab for use in pediatric patients with philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia . August 17, 2017: FDA approval of Inotuzumab Ozogamicin (InO) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia . Both agents moved forward in current COG approach to relapsed ALL

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 28 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Kayla

Relapse #2: 03/2017 (cont) Protocol : Eligible for AALL1621 Phase II trial with InO Next steps: Consent and assent obtained Starts Cycle #1 of InO Included consult to PACT (pediatric advanced care team)

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 29 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

AALL1621

Primary Aim: To determine The morphologic response rate following one cycle of treatment with InO in children with relapsed or refractory CD22+ B cell ALL

Secondary Aims: To determine • SAFETY of single agent InO administered at the adult recommended dose to pediatric patients with relapsed or refractory CD22+ B lineage ALL • Incidence, severity and outcomes of SOS/VOD of the liver in patients during InO therapy and following subsequent treatment including HSCT

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Let’s Compare

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 31 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Phase/Endpoints/Blina vs. InO

Blina InO Phase III Phase II First Relapse Second or Greater Relapse/Refractory Disease END Point 5 yr OS Response post cycle 1

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 32 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Toxicity Blina vs. InO

Blina InO CRS • Associated with high leukemic burden VOD/SOS • Minimize hepatotoxic meds • Range from mild to severe and life-threatening • Prophylaxis with UCDA • Highest risk: 1st cycle and first 72 hrs of infusion -Hx of prior HSCT • Grade 3-4 – stop Blina and consider Tociluzumab -Anticipated HSCT post InO Neuro- • Mild tremor to seizures • S/S -RUQ pain toxicity STOP Blina if seizures occur! • Daily handwriting test/sticker chart -Jaundice -Edema/Ascites -Rapid weight gain

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Administration: Blina versus InO

Blina InO Infusion • 28 day continuous infusion • Weekly 60 min IV Infusion – 3 doses/per cycle Pump/Bags • Low infusion rate outpatient pump • Hospital IV pump • Change bag q 96 hrs PFE • Significant for: • No home administration/management -care post discharge/symptom management • Toxicity/symptom management review -pump and administration safety and toxicity Hospitalization • 3 days with first cycle and • Not required • 2 days with subsequent cycles • Recommend 1st dose of cycle 1 as HR of TLS Premedication • Steroids • Antipyretics, antihistamines and corticosteroid – 30-60 minutes prior to ↓CRS incidence to prevent infusion reactions

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 34 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Blinatumomab

COG Nursing Vimeo Site! • More detailed information about Blinatumomab and AALL1331 • www.https://vimeo.com/cognursing

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 35 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Chemotherapy (UKALLR3 Blocks) or MAB UKALLR3-Chemo MABS- Blina/InO Block 2 Block 3 Blinatumomab DEX DEX VCR VCR Cycle 1 MTX ARAC Cycle 2 IT chemo Erwinia PEG ASP ASP Inotuzumab CPM MTX VP16 Cycle 1 Cycle 2

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 36 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Audience Participation

Do you feel that your hospital is well prepared for administering Blinatumomab to your patients? a) Yes b) No

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Audience Participation

When a patient is discharged from your hospital after the initial administration period for Blinatumomab, where is the follow-up care provided for your patients and families during the additional days of the infusion (bag and tubing changes, trouble-shooting, etc)? a) Care provided in the hospital, outpatient clinic or infusion center b) Care provided by home care agency c) Care is provided by both

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 38 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Audience Participation

With patients receiving Blinatumomab, does your institution require that patients stay within a certain distance of the hospital to address unexpected bag/tubing issues, pump issues or toxicities? a) < 60 minutes away b) <90 minutes away c) < 2 hours away d) No requirements

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 39 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Blinatumomab – Lessons We’ve Learned

Illustration by Alice Yang, 2011

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 40 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Blina: Lessons Learned . Central Lines ♦ Flush policies ♦ Fever management . Pumps ♦ Access ♦ CADD • Recommended both for inpatient and outpatient delivery • Develop a plan for after hours management for “pump” problems . Burden of Care ♦ Distance to hospital • Management of toxicity • Pump/administration concerns ♦ Family will need to monitor/manage

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 41 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Lessons Learned from Blina…so far . No solution fits every center! . Consider how your institution will prepare and plan! . Consider building “action plans” into your standard operating procedures (SOPs) ♦ Example: Deviation from Flush Policy for Central Lines ♦ Example: Deviation from Management of Fever Policy with Cycle 1 Blina ♦ Protocol for Families for “after hours” pump related concerns . Timing of Blina ♦ Blina start time for best outpatient bag changes (ex. Aim for 12-2pm) . Back Up Blina Bags ♦ Bags prepared in advance “back-up bags” – ready for quick change, ready in event of Blina interruptions requiring hanging of new bag

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Example

43 Used with permission from SickKids, 2018

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 43 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

Kayla

Post cycle #1 InO BMA/Bx: Remission and MRD negative Plan: Consolidate remission with additional cycle of InO Prepare for HSCT after second cycle of InO

C211_A Tale of Two MoABs: Blinatumomab and Inotuzumab in COG Clinical Trials for Relapsed B-ALL 44 Thursday, September 13, 2018 COG Track at APHON 4:45PM-5:45PM

MABs: Blina and InO…and maybe more! . Offers hope! ♦ Are we seeing a new experience where relapsed B ALL is somewhat of a chronic condition? ♦ How will we support patients and their families in this “new world”? . Unique toxicities: Consider how to educate and have an action plan! ♦ Mitigate and manage expected toxicities ♦ Provide anticipatory guidance to patients and families . New considerations for late effects with immunotherapy! What will we see in our survivors? ♦ How will Long Term Follow-up for survivors change?

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Questions/Discussions

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Abbreviations FULL TERM ABBREVIATION Acute lymphoblastic leukemia ALL Also Known As AKA Asparaginase ASP Association of Pediatric Hematology/Oncology Nurses APHON Autism Spectrum Disorder ASD Bi-specific T-cell Engager BiTE Blinatumomab Blina Bone marrow aspirate BMA Bone marrow aspirate/biopsy BMA/BX Central nervous system CNS Chemotherapy Chemo

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Abbreviations FULL TERM ABBREVIATION Children's Oncology Group COG Chimeric antigen receptorT-cell CART Cluster of differentiation CD Complete blood count CBC Complete Remission CR Computerised Ambulatory Delivery Device CADD Cryoprecipitate Cryo Cyclophosphamide CPM Cytarabine ARAC Cytokine release syndrome CRS Deoxyribonucleic acid DNA Dexamethasone DEX

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Abbreviations FULL TERM ABBREVIATION Diagnosis Dx Disease Free Survival DFS End of Induction EOI Etoposide VP16 Fedral Drug Agency FDA Fresh frozen plasma FFP Gastrointestinal GI Headache HA Hematopoeitic stem cell transplant HSCT High risk HR Hours hrs

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Abbreviations FULL TERM ABBREVIATION Inotuzumab InO Interleukin-2 IL-2 Intrathecal IT Intravenous IV Intravenous fluid(s) IVF(s) Liver function test(s) LFT(s) Major Histocompatability Complex MHC Matched related donor MRD Methotrexate MTX Microgram mcg Minimal residual disease MRD Monoclonal antibody/antibodies MoAb(s)

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Abbreviations FULL TERM ABBREVIATION Months mos Negative Neg Neurological Neuro Number N One thousand K Overall survival OS Oxygen O2 Pediatric advanced care team PACT PEG-Asparaginase PEG Radiation therapy XRT Right upper quadrant RUQ Signs and symptoms S/S

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Abbreviations FULL TERM ABBREVIATION Sinusoidal obstruction syndrome SOS Standard Operating Procedure(s) SOP(s) T cell receptor TCR Tumor Associated Antigens TAA Tumor lysis syndrome TLS Ursodeoxycholic acid UCDA Venous occlusive disease VOD Vincristine VCR White blood count WBC Year(s) yr(s)

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References

. Bhojwani, D., (2017) Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL), Journal of Clinical Oncology, 35,suppl. 15. . Kantarjian, H., (2016) Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia, New England Journal of Medicine, 375(8) . Nguyen, K., Devidas, M., Cheng, SC et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children’s Oncology Group study, Leukemia (2008), 22, 2142-2150 . Porter, D., (2014) ASH abstract, December . Teachy, DT, Rheingold, SR, Maude, SL, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy, Blood (2013), 121: 5154-5157 . Von Stackeklberg, A. (2016) Phase I/Phase II Study of Blinatumomab in Pediatric Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia, Journal of Clinical Oncology, 34

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