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Thursday, April 22, 20215:00 PM – 6:30 PM ET

A presentation timeslot has been assigned to provide a symposium supported by

The Leukemia & Lymphoma Society during the Oncology Nursing Society’s (ONS)

Congress Virtual Event. The Oncology Nursing Society's assignment of a presentation

timeslot does not imply product endorsement.

GENOMICS AND HEMATOLOGIC MALIGNANCIES:

BEYOND THE PHILADELPHIA CHROMOSOME

Patricia Friend, PhD, APRN-CNS, AOCNS, AGN-BC

Eric Zack, DNP, RN, ACNP-BC, AOCN, BMTCN

THE LEUKEMIA & LYMPHOMA SOCIETY (LLS)

SUPPORTING & EDUCATING NURSES & YOUR PATIENTS

Lauren Berger, MPH

Senior Director, Professional Education & Engagement

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CE DESIGNATION

Approval for nurses has been obtained by the National Office

of The Leukemia & Lymphoma Society under Provider

Number CEP 5832 to award 1.5 continuing education contact

hours through the California Board of Registered Nursing.

LEARNING OBJECTIVES

At the conclusion of this program, participants will be able to:

• Discuss foundational genomic concepts (DNA, gene, chromosome, somatic and germline genomic variants)

• Discuss and define biomarkers and biomarker testing

• Identify appropriate biomarker (genomic) testing for hematologic cancers across the care continuum (diagnosis, prognosis, treatment, disease monitoring)

• Describe the role of the nurse, APRN, and others on the healthcare team in preparing patients and caregivers for biomarker testing, including access and financial implications

• Identify resources to educate and support patients and caregivers regarding biomarker testing

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OUR MISSION

The mission of The Leukemia & Lymphoma

Society (LLS) is: Cure leukemia, lymphoma,

Hodgkin's disease and myeloma, and improve

the quality of life of patients and their families.

We fund RESEARCH to advance lifesaving treatments

We drive ADVOCACY for policies that protect patient

access to lifesaving treatment

We provide patients and families with hope, guidance,

education and SUPPORT

LLS - YOUR BLOOD CANCER CONTINUING EDUCATION (CE) DESTINATION

▪ Webinars offering free CE credit www.LLS.org/CE

- GENOM: Genomics Essentials in Hem/Malignancies

- CAR T-cell Therapy: A Road Map

- Hematopoietic Cell Transplantation

- Blood Cancer 101

- Blood Cancers – Disease Specific

▪ Facts Sheets for HCPs www.LLS.org/CE

- Biomarker Testing (Molecular Profiling)

- Measurable Residual Disease

- CAR T-cell Therapy

- AML

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Treating Blood Cancers: Podcasts for HCPs

Conversations with experts about diagnosing & treating

blood cancers www.LLS.org/HCPpodcast

Recent episodes:

- Updates in CAR T-cell Therapy

- The COVID-19 Vaccine and Your Patient with Cancer

- What’s New in Treatment for AML

- Managing Treatment for Patients with R/R Lymphoma

- Communicating with Caregivers: Strategies for HCPs

- A Deeper Dive into MRD

www.LLS.org/CE

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LLS RESOURCES FOR PATIENTS AND CAREGIVERS

Disease, treatment and support:

❑ Webinars - www.LLS.org/programs

❑ Booklets - www.LLS.org/booklets

❑ Podcasts - www.LLS.org/podcast

LLS RESOURCES FOR PATIENTS AND CAREGIVERS

❑ Information Specialists – one-on-one information & support on treatment, financial and psychosocial

resources. Also send free materials to patients & HCPs

❑ Nutrition Consultations – One-on-one consultations from certified dietitian

❑ Clinical Trial Nurse Navigators – RNs with expertise in blood cancers work one-on-one with patients,

caregivers or HCPs, or You can Refer a patient www.LLS.org/CTSCreferral

An extension of your team, providing support to you & your patients: M - F, 9 am to 9 pm ET:

❑ Phone: (800) 955-4572

❑ Live chat: www.LLS.org/IRC

❑ Email: infocenter@LLS.org

❑ Refer your patient for support: www.LLS.org/HCPreferral

Additional support for patients & caregivers – www.LLS.org/Support

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FACULTY

Patricia Friend, PhD, APRN-CNS, AOCNS, AGN-BC

Associate Professor and Program Director

Marcella Niehoff School of Nursing

Loyola University Chicago

Maywood, IL

Eric Zack, DNP, RN, ACNP-BC, AOCN, BMTCN

RN3 (Staff/Charge Nurse)

Inpatient Hematology/HSCT unit

Rush University Medical Center

Assistant Professor

Marcella Niehoff School of Nursing

Loyola University Chicago

Maywood, IL

FACULTY DISCLOSURES

Patricia Friend, PhD, APRN-CNS, AOCNS, AGN-BC

Has no financial disclosures.

Eric Zack, DNP, RN, ACNP-BC, AOCN, BMTCN

Has a financial interest/relationship or affiliation:

honoraria/consulting fee for Careview, a testicular cancer patient app.

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Polling Question 1

Which of the following statements most resembles your knowledge and experience with genomics?

• I have had my dog’s DNA sequenced• I understand genetics better in cold weather when I put my

codon• I once took a DNA test. It was pretty difficult, but I think I passed• Since the pandemic, I have been unable to put on my skinny

genes

https://youtu.be/5kAL11m_fwM

05 FEBRUARY 2021

VOL 371, ISSUE 6529

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Polling Question 2

Precision oncology utilizes genomic information of the individual and of the tumor to personalize risk identification, diagnosis and treatment.

a. True

b. False

Significance

• Genomics and precision approaches revolutionizing cancer care

• Nurses will be at the forefront of translating and applying genomic discoveries to patients, families, public etc.

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Background and Significance

• Rapid advances in genomic technologies

• Improved understanding of the genomic architecture of cancer

• New paradigms to prevent, diagnose, treat, and manage cancer and cancer symptoms

• Complex inconsistently used terms

• Confusion and literacy deficits

o Patients/families

o All healthcare providers

• Increased risk for error (germline or testing for inherited cancers)

• Missed opportunities for precision treatment (access to biomarker or somatic testing of the tumor)

• Impacts opportunities to improve health outcomes

CML and the Philadelphia Chromosome

• BCR-ABL discovered in 1960

• Imatinib (Gleevec®) approved in 2001

• Use of highly sensitive PCR to detect and monitor

• Possibility of “cure” and stopping TKIs

• Only cure used to be allo-SCT

• Success with GIST, move to tumor-agnostic approach

Sampaio et al., (2021). Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review. World Journal of Clinical Oncology, 12(2), 69–94. https://doi.org/10.5306/wjco.v12.i2.69Rosas, D., & Raez, L. E. (2020). Review of the Agnostic-Type Treatment Approach: Treating Cancer by Mutations, Not by Location. Oncology and therapy, 8(1), 59–66. https://doi.org/10.1007/s40487-020-00114-4

May 28, 2001

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https://www.cancer.gov/types/leukemia/patient/cml-treatment-pdq

Polling Question 3

Chromosomes are suitcases that contain tightly coiled DNA:

a. True

b. False

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Foundational Genomic Concepts

• DNA

• Genes

• Chromosomes

Genetic or Genomic? Does It Matter?

• Genetic: inheritance of genes (classic Mendelian single gene disorders) and study of individual genes

• Genomic: study of all genes and interactions among each other and with the environment (complex disease)

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Polling Question 4

DNA “sequence” refers to the order of:

a. Nucleotides

b. Genes

c. Chromosomes

d. Proteins

e. RNA

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Image created by the National Institute of Health. Retrieved from https://www.genome.gov/about-genomics/fact-sheets/Deoxyribonucleic-Acid-Fact-Sheet

https://www.genome.gov/genetics-glossary/Chromosome

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https://www.genome.gov/about-genomics/fact-sheets/Chromosomes-Fact-Sheet

All chromosomes underlined in red constitute the autosomes.

The chromosomes circled in green are the sex chromosomes

Karyotype:

visual

representation

of

chromosomes

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https://www.genome.gov/about-genomics/fact-sheets/Chromosome-Abnormalities-Fact-Sheet

Polling Question 5

Which term best represents an inherited alteration in a person’s DNA that directly contributes to the development of disease?

a. Variant

b. Mutation

c. Germline Pathogenic variant

d. Somatic alteration

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What Is a Genomic Variant?

https://www.genome.gov/Health/Genomics-and-Medicine/Polygenic-risk-scores#one

Basic Concepts

Received permission to use this image from Myriad https://myriad.com/

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Polling Question 6

Which of the following statements regarding the BRCA1 gene is correct?

a. The BRCA1 gene is only found in families with a history of breast and ovarian cancer.

b. The BRCA1 gene is present in everyone’s DNA

c. The BRCA1 gene is only carried by females in families with breast and ovarian cancer

Image created by the National Institute of Health. Retrieved from https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-changes-infographic

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Epigenetic Modification

https://www.hematology.org/research/ash-agenda-for-hematology-research/epigenetic-mechanisms

Polling Question 7

All cancer is genetic but not all cancer is inherited:

a. True

b. False

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Received permission to use this image from Myriad https://myriad.com/

Received permission to use this image from Myriad https://myriad.com/

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GermlineInherited

Classified according to pathogenicity

Variant ClassificationGermline and somatic

variants are considered biomarkers. The term

“variant” is increasingly being used in place of the

term “mutation”

SomaticAcquired

Identified from the tumor

Classified according to actionability or druggability, as well as if they are drivers of the

oncogenic process or passengers

Polling Question 8

Which of the following is considered a biomarker?

a. PSA

b. HER2

c. EGFR

d. FLT-3

e. All of the above

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What Is a Biomarker?

A biomarker refers to a quantifiable biological parameter that is measured and evaluated as an indicator of normal biological, pathogenic, or pharmacologic responses to a therapeutic intervention.

FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource. Bethesda, Maryland: Food and Drug Administration-National Institutes of Health Biomarker Working Group; 2016. https://www.ncbi.nlm.nih.gov/pubmed/27010052.

Why Are Biomarkers So Important in Cancer Care?

• The massive paradigm shift in cancer care toward precision and targeted therapies includes rapidly evolving use of biomarkers and biomarker testing applied throughout the cancer care continuum.

• Increasingly, genomic markers, such as germline and tumor gene variants, and patterns of gene expression are used to guide selection of targeted therapies and identification of inherited risk.

• Rapidly changing recommendations and increasing knowledge of various actionable biomarkers in cancer care are significant challenges for providers.

• Standardization of terms is critical for optimal management

• Latest recommendations for biomarker testing and optimal therapy are underutilized in community practices

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Similar Terms: Biomarker and Biomarker Testing

• Tumor marker

• Genomic alteration

• Variant (mutation)

• DTC marketing say “mutation”

• Technically, both germline and somatic variants are considered biomarkers, but the term is mostly associated with somatic variants

• Genomic profiling, somatic tumor profiling, molecular profiling, tumor testing are terms used interchangeably, but confusing for patients and families

Categories of Biomarkers

National Center for Biotechnology Information: BEST (Biomarkers, Endpoints, and other Tools) Resource, https://www.ncbi.nlm.nih.gov/books/NBK338448/#IX-S

https://www.fda.gov/files/BIOMARKER-TERMINOLOGY--SPEAKING-THE-SAME-LANGUAGE.pdf

• Susceptibility/risk• Diagnostic• Monitoring• Prognostic• Predictive• Pharmacodynamic/response• Safety

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Classification Examples

Susceptibility/Risk Germline BRCA1 pathogenic variant (PV)

Diagnostic HER2 expression in breast cancer

Monitoring BCR-ABL fusion protein in CML

Prognostic Oncotype DX®

Predictive Somatic BRCA driver variant eligible for treatment

with PARP inhibitor

Pharmacodynamic 18F-FES, labeled nucleotide that correlates with ER

expression

Safety UGT1A1 genotyping for allele versions that

increase risk of irinotecan-induced toxicities

https://www.commoncancertestingterms.org/files/Consistent-Testing-Terminology-Whitepaper-070720.pdf

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Image created by the National Institute of Health. Retrieved from https://www.genome.gov/19516567/

Why Is Testing Being Done?

• Prevention (identify hereditary syndromes/inherited risk)

• Diagnostic

• Prognostic

• Predictive

• Therapeutic (to direct therapy to actionable variants)

• Pharmacogenomics

• Detect variation (DTC)

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What Is Analyzed? How Is it Tested?• Analytes

• DNA

• RNA

• Protein

• Obtained from

• tissue or liquid biopsy

• Tested by (traditional methods)• IHC• FISH• PCR• Flow cytometry

• Genomic/DNA Sequencing, detects variations in the sequence, structure, or expression of DNA and RNA

• Single gene (Sanger Sequencing)• Next generation sequencing (NGS), multiple genes simultaneously

When to Test

• Across the cancer continuum: early detection (cancer interception), risk identification, at diagnosis, treatment selection, treatment failure, metastatic progression/recurrence detection (MRD),

• Testing is biomarker and disease-specific (e.g., BRAF somatic variant in melanoma is quite consistent from primary to metastasis to progression), such that repeated biomarker testing for this variant may not be necessary. However, EGRF in NSCLC changes and newer acquired variants after treatment may indicate acquired treatment resistance and need to change therapy.

• In hematological malignancies, testing is done throughout the disease continuum as a measure of treatment response and for minimal residual disease (MRD) monitoring

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Hallmarks of Cancer and Associated Biomarkers

Bedard, P. L., Hyman, D. M., Davids, M. S., & Siu, L. L. (2020). Small molecules, big impact: 20 years of targeted therapy in oncology. Lancet, 395(10229), 1078–1088. https://doi.org/10.1016/S0140-6736(20)30164-1

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Biomarker Full Name Function Effect

Acute Myeloid Leukemia (AML)

• About 20,240 people in the United States will be diagnosed with AML in 2021, and 11,400 deaths are estimated in 2021 (https://www.cancer.gov/types/leukemia/hp/adult-aml-treatment-pdq)

• Increased risk with increasing age

• Most common acute leukemia affecting adults (incidence increases significantly after 55 years old)

• Second most common leukemia

• AML makes up 32% of all adult leukemia cases

• 5-year survival only 28.7%

SEER. (2021). Cancer stat facts: Leukemia — Acute myeloid leukemia (AML) 2010-2016 SEER. Accessed April 14, 2021 from https://seer.cancer.gov/statfacts/html/amyl.html

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Hematopoiesis

Wikipedia. (2021). Haematopoiesis. Accessed on April 16, 2021 from https://en.wikipedia.org/wiki/Haematopoiesis

AML Case Study

• 75-year-old male

• PMH: HTN, chronic low back pain

• CC: Pancytopenia on routine laboratory studies

• S/S: Subsequently developed progressive fatigue & hematochezia

• Presented to ED and laboratory studies were notable for pancytopenia with peripheral blasts

• Bone marrow biopsy/aspirate consistent with acute myeloid leukemia

• Normal male karyotype, FLT3 negative

• NGS Gene Panel: ACTA2, FANCC, IDH2, PALLD, SRSF2, TET2

• Received induction chemotherapy with high dose cytarabine & mitoxantrone (dose reduced for age)

• Day 14 bone marrow biopsy/aspirate with persistent leukemia

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FINAL DIAGNOSISA&B. (RPIC) Bone marrow, aspirate, core biospy, touch prep AND peripheral blood:- ACUTE MYELOID LEUKEMIA, EXTENSIVE INVOLVEMENT (SEE COMMENT)

AML Pathophysiology & Genomic Testing• Class I variants – myeloproliferation of abnormal WBCs

• Genes coding for receptor & non-receptors• Protein tyrosine kinases

• FLT3, JAK2, C-KIT, ABL1

• Genes coding for proteins of GTPase activity• N-RAS, K-RAS

• Class II variants – differentiation arrest

• Genes of transcription factors

• Chromosomal aberrations –gene fusion• CBF, MLL, EVI1, TEL, & RARA

• Point mutations• CEBPA, NPM1

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Polling Question 9

FLT 3 negative is a favorable or good prognostic biomarker?

a. True

b. False

ARUP Consult. (2021). Acute myeloid leukemia molecular genetic testing. Accessed April 14, 2021 from https://arupconsult.com/ati/acute-myeloid-leukemia-molecular-genetic-testing

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Genomic Risk Classification in AML

Voso, M. T., Ottone, T., Lavorgna, S., Venditti, A., Maurillo, L., Lo-Coco, F., & Buccisano, F. (2019) MRD in AML: the role of new techniques. Frontiers in Oncology, 9, 655. https://doi.org/10.3389/fonc.2019.00655

Diagnostic Platforms to Comprehensively Identify the Appropriate Targets

The Blue Matter Team (2019). Oncology trends: Is past performance predictive of future returns? – Part I, trends overview. Accessed April 14, 2021 from https://bluematterconsulting.com/oncology-trends-part-i-overview/

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https://www.foundationmedicine.com/test/foundationone-heme

Genomic Testing to Diagnose AML

• Cytogenetic analysis (karyotyping)

• Fluorescence in Situ Hybridization (FISH)

• Molecular testing- Polymerase Chain Reaction (PCR)

- DNA Sequencing

- Next-Generation Sequencing (NGS)

• Liquid Biopsy (near future)

Patient Empowerment Network (2021). AML genetic testing explained. Accessed April 14, 2021 fromhttps://powerfulpatients.org/2019/08/21/genetic-testing-explained/

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Trino et al., (2021). Clinical relevance of extracellular vesicles in hematological neoplasms: from liquid biopsy to cell biopsy. Leukemia, 35(3), 661–678. https://doi.org/10.1038/s41375-020-01104-1

Biomarkers of Disease and Therapeutic Targets

Khalife, J., Sanchez, J. F., & Pichiorri, F. (2020) Extracellular vesicles in hematological malignancies: from biomarkers to therapeutic tools. Diagnostics (Basel, Switzerland), 10 (12), 1065. https://doi.org/10.3390/diagnostics10121065

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AML — Malignancy-Derived Extracellular Vesicles (EVs) as Biomarkers of Disease and Therapeutic Targets

Hematological Malignancies EV Content Biomarker Use Therapeutic Targets

AML

NPM1, FLT3-ITD mRNAs Prognosis Yes

MCL-1, BCL-2, BCL-XL Drug resistance Yes

CXCR4, IGF-IR mRNAs No Yes

CD33, CD34, CD117 Diagnosis Not Indicated

TGFβ1 Diagnosis, drug resistance Yes

CD13 Disease progression Not Indicated

let-7a, miR-99b, miR-146a, miR-191, miR-1246, miR-10b

Diagnosis, prognosis Yes

miR-155Diagnosis, prognosis,

drug resistanceYes

Khalife, J., Sanchez, J. F., & Pichiorri, F. (2020). Extracellular vesicles in hematological malignancies: from biomarkers to therapeutic tools. Diagnostics (Basel, Switzerland), 10(12), 1065. https://doi.org/10.3390/diagnostics10121065

Treatment Targets for AML

Bohl, S. R., Bullinger, L., & Rücker, F. G. (2019). New targeted agents in acute myeloid leukemia: new hope on the rise. Int J Mol Sci, 20(8), 1983. https://doi.org/10.3390/ijms20081983

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https://www.lls.org/blog/precision-medicine-hope-and-hype-asco18

FDA-Approved Targeted Treatments for AML

• Anti-CD33 antibody - gemtuzumab ozogamicin (GO)

• FLT-3 Inhibitors - sorafenib, midostaurin, quizartinib, crenolanib, gilteritinib

• IDH inhibitors - enasidenib, ivosidenib

• Hedgehog inhibition - glasdegib

• BCL2 inhibition - venetoclax

• DNA methyltransferase (DNMT) inhibitor – azacytidine & decitabine

https://www.cancer.gov/about-cancer/treatment/drugs/leukemia#3 ; https://jhoonline.biomedcentral.com/track/pdf/10.1186/s13045-019-0774-x.pdf

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Treatment Targets for AML

Bohl, S. R., Bullinger, L., & Rücker, F. G. (2019) New targeted agents in acute myeloid leukemia: new hope on the rise. Int J Mol Sci, 20(8), 1983. https://doi.org/10.3390/ijms20081983

Epigenetic Modification and Role of Methylation and Acetylation

https://courses.lumenlearning.com/wm-biology1/chapter/reading-eukaryotic-epigenetic-gene-regulation/

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AML Measurable Residual Disease Flow Panel

• Markers: cCD3, CD11b, CD13, CD14, CD16, CD19, cCD22, CD33, CD34, CD45, CD64, cCD79a, CD117, CD123, HLA-DR, cMPO, & nTdT

(17 markers)

• Sources: Bone marrow aspirate, peripheral blood, fresh bone marrow core biopsy, fresh/unfixed tissue, & fluids & FNAs

NeoGenomics. (2021). AML follow-up flow panel. Accessed April 14, 2021, from https://neogenomics.com/test-menu/aml-follow-flow-panel

Monitoring for Measurable Residual Disease in AML

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865231/table/T3/?report=objectonly

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AML Case Study Resolution

• Treated with enasidenib 100 mg PO daily

• Restaging bone marrow biopsy/aspirate two months after initiation of enasidenibtherapy with findings of normocellular marrow with trilineage hematopoiesis

• No morphological or flow cytometric evidence of residual AML

• Continued on enasidenib for 17 months until laboratory studies with new cytopenias concerning for relapsed disease

• Underwent bone marrow biopsy/aspirate which revealed relapsed acute myeloid leukemia

• Therapeutic options discussed with patient

• Plan to start treatment with decitabine plus venetoclax

Burd, et al. (2020). Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. Nature Medicine, 26(12), 1852–1858. https://doi.org/10.1038/s41591-020-1089-8

www.LLS.org/BeatAML

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CLL Epidemiology

• Most common type of leukemia in adults older than 19-years-old

• About 21,250 people in the United States will be diagnosed with CLL in 2021, and 4320 deaths are estimated in 2021 (https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

• CLL accounts for about one-quarter of the new cases of leukemia

• The average person's lifetime risk of getting CLL is about 1 in 175 (0.57%)

• The risk is slightly higher in men than in women

• CLL mainly affects older adults with the average age at diagnosis at 70 years old

• The survival rate for people with CLL varies widely according to stage

• The 5-year survival rate for people age 20 & older with CLL is 85%

American Cancer Society. (2021). Key statistics for chronic lymphocytic leukemia. Accessed on April 10, 2021 from https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/key-statistics.html

Hematopoiesis

Wikipedia. (2021). Haematopoiesis. Accessed on April 16, 2021 from https://en.wikipedia.org/wiki/Haematopoiesis

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CLL Case Study• 76-year-old female who presents to establish care with leukocytosis, newly diagnosed CLL

(2015)

• CC: Longstanding left lower quadrant/pelvic pain for the last 2.5 years since ovary was removed and fatigue

• Followed by Gyn MD but pt feels pain is related to same, previously treated with premarincream

• She does walk her dog regularly

• PMH: Fibromyalgia treated with pregabalin & gabapentin

• Physical Exam: PHYSICAL EXAM: BP 124/60, Pulse 77, Temp (Tympanic) 97.5 °F (36.4 °C), Resp 20, Ht 160 cm (5' 2.99"), Wt 96.616 kg (213 lb), BMI 37.74 kg/m2, SpO2 96%

• CLL work-up initiated

• BM biopsy showed 87% involvement by CLL

• Creatinine clearance approximately 40ml/min

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Polling Question 10

Somatically altered deletion of TP53 is an actionable biomarker?

a. True

b. False

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CLL Pathophysiology & Genomic Testing • ZAP-70

• CD 38

• del (13q)

• Trisomy 12

• del (11q)

• del (17p)

• NOTCH1 mutations

• SF3B1 mutations

• TP53 abnormalities

• MYD88 mutations

• IGVH status (changed or mutated vs. unchanged or unmutated)

Cancer.Net. (2021). Leukemia - Chronic lymphocytic - CLL: Diagnosis. Accessed April 14, 2021, from https://www.cancer.net/cancer-types/leukemia-chronic-lymphocytic-cll/diagnosis

Prognostic Biomarkers in CLL

Parker, T. L., & Strout, M. P. (2011). Chronic lymphocytic leukemia: prognostic factors and impact on treatment. Discovery Med, 11(57), 115–123.

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Older & Newer Prognostic Factors in Patients with CLL

Rai, Kanti. (2015). Chronic lymphocytic leukemia (CLL)—Then and now. Accessed April 14, 2021, from https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.24282

National Comprehensive Cancer Network (2021). available at www.nccn.org

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Genetic Lesions in CLL Clonal Evolution and Richter Transformation

Moia, R., Patriarca, A., Deambrogi, C., Rasi, S., Favini, C., Kodipad, A. A., Schipani, M., & Gaidano, G. (2020) An update on: molecular genetics of high-risk chronic lymphocytic leukemia. Expert Rev Hematol, 13(2), 109–116. https://doi.org/10.1080/17474086.2020.1697225

CLL — Malignancy-Derived Extracellular Vesicles (EV) as Biomarkers of Disease and Therapeutic Targets

Hematological Malignancies EV Content Biomarker Use Therapeutic Targets

CLL

CD5, CD31, CD44, CD55, CD62L, CD82, HLA-A,

HLA-B, HLA-C, HLA-DRDiagnosis Not Indicated

CD19, CD37 Disease progression Yes

CD52Disease progression,

drug resistanceNo

CLL

miR-150, miR-155 Diagnosis, Prognosis Yes

CCL3/4, EGR1/2/3, c-Myc

Drug resistance Yes

miR-19bDiagnosis of RS,

multidrug therapy resistance

Yes

Khalife, J., Sanchez, J. F., & Pichiorri, F. (2020). Extracellular vesicles in hematological malignancies: from biomarkers to therapeutic tools. Diagnostics (Basel, Switzerland), 10(12), 1065. https://doi.org/10.3390/diagnostics10121065

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FDA-Approved Treatments for CLL

FDA-Approved Targeted Treatments for CLL• Anti-CD19 & anti-CD3 antibodies - blinatumomab

• Anti-CD20 antibody - rituximab & its biosimilars, ofatumumab, obinutuzumab, ocaratuzumab, & veltuzumab

• Anti-CD22 antibody - epratuzumab, inotuzumab ozogamicin

• Anti-CD33 antibody - gemtuzumab

• Anti-CD52 antibody - alemtuzumab

• BTK inhibitor - ibrutinib, acalabrutinib

• BTK and PI3k inhibitor - idelalisib

• BCR and PI3k inhibitor - duvelisib

• BCL-2 antagonist - venetoclax

• FLT3 Inhibitor - midostaurin, gilteritinib

• SMO - glasdegib

• IDH inhibitor - enasidenib, ivosidenib

• SYK inhibitor - fostamatinib disodium

National Institute of Health: National Cancer Institute. (2021). Drugs approved for leukemia. Accessed April 14, 2021, from https://www.cancer.gov/about-cancer/treatment/drugs/leukemia#3

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Treatment Targets for CLL

Burger, J. A., & O'Brien, S. (2018) Evolution of CLL treatment - from chemoimmunotherapy to targeted and individualized therapy. Nat Rev Clin Oncol, 15(8), 510–527. https://doi.org/10.1038/s41571-018-0037-8

Fürstenau M, Hallek M, Eichhorst B. Sequential and combination treatments with novel agents in chronic lymphocytic leukemia. Haematologica. 2019 Nov;104(11):2144-2154. doi: 10.3324/haematol.2018.208603. Epub 2019 Oct 4. PMID: 31585959; PMCID: PMC6821614.

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Monitoring for Measurable Residual Disease in CLL

Fürstenau, M., De Silva, N., Eichhorst, B., & Hallek, M. (2019). Minimal residual disease assessment in CLL: ready for use in clinical routine? HemaSphere 3(5):e287. https://doi.org/10.1097/HS9.0000000000000287

CLL Case Study Resolution

• The patient started treatment with ibrutinib 420mg once daily in August 2017

• She has experienced an increase in WBC after starting therapy as expected with continued subtle downward trend

• No significant changes in HGB or platelet count

• Reported symptoms of unintentional weight loss & overwhelming fatigue (February 2018)

• Initial concern for disease progression &/or transformation

• However, CT scans were without lymphadenopathy, WBC continued to downtrend, & LDHwas within normal limits

• Recommended to increase PO intake to accurately assess ibrutinib's effect on diarrhea & means of weight loss

• Encouraged to re-establish with psychologist as her depression is likely playing a role in fatigue/decreased appetite

• These symptoms have since improved

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The Future: Cancer Genomics Report

Duncavage, E. J., Schroeder, M. C., O'Laughlin, M., Wilson, R., MacMillan, S., Bohannon, A., Kruchowski, S., Garza, J., Du, F., Hughes, A., Robinson, J., Hughes, E., Heath, S. E., Baty, J. D., Neidich, J., Christopher, M. J., Jacoby, M. A., Uy, G. L., Fulton, R. S., Miller, C. A., … Spencer, D. H. (2021). Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers. The New England Journal of Medicine, 384(10), 924–935. https://doi.org/10.1056/NEJMoa2024534

Nangalia, J., & Campbell, P. J. (2019). Genome Sequencing during a Patient's Journey through Cancer. The New England Journal of Medicine, 381(22), 2145–2156. https://doi.org/10.1056/NEJMra1910138

Nursing Implications

Vorderstrasse AA et al. Personalizing patient care with precision medicine. Semin Oncol Nurs 2014;30(2):130–136.

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Polling Question 11

My ability to discuss genomics with patients and families is:

a. Very competent

b. Competent

c. Somewhat competent

Patient Points

• Start with basics

• Use visual analogies

• Clear consistent language: terminology matters

• Teach back

• What questions have you heard from patients and families?

• Costs of testing? Costs of treatment with targeted agents?

• Leverage expertise of entire interprofessional team

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https://lungevity.org/sites/default/files/request-materials/LUNGevity-biomarker-testing-booklet-112817.pdf

Use or develop

patient-facing

educational materials

Whitley, K. V., Tueller, J. A., & Weber, K. S. (2020) Genomics education in the era of personal genomics: academic, professional, and public considerations. Int J Mol Sci, 21(3), 768. https://doi.org/10.3390/ijms21030768

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Links/Resources

• https://learn.genetics.utah.edu/content/labs/

• https://www.ashg.org/discover-genetics/

• https://www.jax.org/education-and-learning/clinical-and-continuing-education/ccep-non-cancer-resources/genetic-testing-methods

• https://www.ncbi.nlm.nih.gov/books/NBK279899/

• https://www.mycancergenome.org/

• https://www.illumina.com/areas-of-interest/cancer/research/sequencing-methods.html

• https://www.pathlms.com/ashg/courses/6130

Educational Resources

• http://learn.genetics.utah.edu/

• http://www.g-2-c-2.org/blocks/pla/index.php

• http://www.gepn.cchmc.org (self-paced genetics modules based on NCHPEG competencies)

• http://www.genome.gov/ (National Institutes of Health site)

• http://www.ncbi.nlm.nih.gov/sites/GeneTests/?db=GeneTests(NIH-sponsored site maintained by the University of Washington)

• http://gsic.genetics.utah.edu/ (The University of Utah, Genetic Science Learning Center)

• http://ghr.nlm.nih.gov/ (Genetics Home Reference, a National Library of Medicine site)

• http://www.jaxge.org/portfolio

• http://genomicsintegration.net/index.php

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What Will You Do to Improve Your Genomic Literacy?

We have one goal: A world without blood cancers

THANK YOU

WWW.LLS.ORG/CE

WWW.LLS.ORG/HCPREFERRAL

WWW.LLS.ORG

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