Myeloma Magazine | Spring 2016

A PUBLICATION OF

UAMS MYELOMA INSTITUTE

SPRING 2016

expanding knowledge

Working towards better outcomes

Dear Readers, The world of myeloma research is undergoing exciting advances that are changing the landscape of diagnosis and therapeutic interventions.

With new drug development, creative combinations of drugs, “I invite you to embrace both the reality and further prospect of a cure.”

increased understanding of how the body’s immune system can be harnessed, and the ability to define each patient’s disease at the molecular level, we can now offer treatments that specifically target cancer cells while sparing healthy cells. In short, we can move away from the toxic treatments of old to more easily-tolerated and more effective regimens that produce even better outcomes.

The Myeloma Institute’s team of experts is at the forefront of these promising developments. We are pushing the science along avenues that are leading to increased cure rates for more and more patients.

As you read this inaugural issue of Myeloma, I invite you to embrace both the reality and further prospect of a cure that our work, along with the work of our colleagues, is bringing to patients throughout the world.

Cheers and kind regards,

Gareth Morgan, M.D., Ph.D Director, UAMS Myeloma Institute 2

myeloma.uams

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The Myeloma Institute's Approach for Advances and a Cure . . . . . . . . . . . . . . . . . 4 SPRING 2016

Distilling Excellence . . . . . . . . . . . . . . . . . . 8

EDITOR Janet Aronson

New Clinical Trials . . . . . . . . . . . . . . . . . . . 11

CREATIVE DIRECTOR Laurie Shell GRAPHIC DESIGNER Mindy Stout PHOTOGRAPHER Johnpaul Jones

Advancing Cure with CyTOF Technology . . . . . . . . 12 Publication . . . . . . . . . . . . . . . . . . . . . 15 Brian Walker Brings Molecular Genetics Expertise to the Myeloma Institute . . . . . . . . . . . . . . . 16 Research Grant Awarded to Dr. Schinke . . . . . . . . 19

Director UAMS Myeloma Institute Gareth Morgan, M.D., Ph.D Chancellor University of Arkansas for Medical Sciences Dan Rahn, M.D. Myeloma is published twice a year by the Myeloma Institute, University of Arkansas for Medical Sciences 4301 W. Markham St. #816, Little Rock, AR 72205 Phone: (501) 526-2873 myeloma.uams.edu

Fighting Back to Good Health . . . . . . . . . . . .

20

Supporting the Whole Patient . . . . . . . . . . . .

22

On the Cover: Dr. Sharmilan Thanendrarajan and Dr. Faith Davies

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Welcome to the

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20

medical professionals — are well equipped

inaugural issue of

to make informed decisions that support

Myeloma, the journal of

the best possible health for each individual.

the Myeloma Institute

We hope the Myeloma journal will become

at the University of

one of your trusted sources for news and

Arkansas for Medical Sciences.

The goal of Myeloma is to provide timely updates about progress in clinical treatment and research advances, as well as stories and information of general interest.

As a world leader in myeloma and related

authoritative commentary on breakthroughs and treatment trends.

We welcome your comments. Feel free to contact us via email.

Sincerely, Janet Aronson

diseases, we are committed to ensuring

Editor

that patients and those involved in their

AronsonJanetL@uams.edu

care — family, friends, physicians and other myeloma.uams

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The Myeloma Institute’s Approach for

Advancesand aCure

Dr. Frits van Rhee visits with a patient prior to his infusion.

4

myeloma.uams

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I

nnovative translational research has been at the core of the UAMS myeloma program since

its inception in 1989.

Translational research is research that bridges

Over the course of the Total Therapy clinical trials, we have discovered that myeloma is not a single disease, but rather a collection of different molecular subgroups with distinct

basic science with developments in clinical care.

biology, risk status, and clinical outcome. We

Breakthroughs in the laboratory are translated

have shown that our Total Therapy program

rapidly into clinical care applications.

leads to a cure for a significant proportion of

Over the years, the Myeloma Institute’s

low-risk disease patients. In contrast, outcomes

translational research concept has been to

have not significantly improved for high-risk

control the growth of myeloma by dissecting

myeloma, which has a poor prognosis and

and exploiting the molecular and biological

needs innovative therapeutic solutions.

consequences of both the myeloma cell

Therefore, a key focus of our current

and its interaction with the bone marrow

program is on high-risk myeloma, which

microenvironment. Our physician-scientist team

comprises up to 30 percent of newly

has successfully furthered insights in disease

diagnosed myeloma cases, with the

biology, genetics, and the development of new

understanding that lessons learned will be

diagnostic and staging tools, such as MRI and

readily applied to low-risk myeloma for even

PET-CT.

better outcomes in that group.

The structure of our program has afforded breakthrough discoveries, thanks to our large

Our overall research vision encompasses four

patient referral base, long-term follow-up,

main paths:

integrated basic-clinical investigation, availability

1. Identifying the causes of myeloma.

of samples and laboratory correlates in our

• Understand the underlying causes of

database, and statistical power to interpret

myeloma — environmental, genetic, and

findings in the context of historical patients

other.

with comprehensive annotations of the clinical course and therapeutic interventions.

The Myeloma Institute was the first center to achieve truly curative outcomes through our Total Therapy treatment approach. Total

• Design strategies to prevent MGUS (monoclonal gammopathy of undetermined significance) and smoldering myeloma from developing into active myeloma.

• Understand how inherited genetic factors

Therapy incorporates proven effective agents

interact with cancer cells to affect disease

up front for an “all-out attack” on myeloma.

progression, side effects of treatment, and

The idea is to knock out the myeloma cells at

outcome.

the outset, even the tough, resistant cells, and give them no opportunity to survive. The goal

2. Myeloma Stem Cell Biology • Understand how myeloma develops,

is eradication of the myeloma and complete

specifically how MGUS and smoldering

molecular cure.

myeloma transform into myeloma. 

myeloma.uams

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• Gain insight into the biology of high-risk myeloma and treatment resistance.

• Design new treatments aimed at the biology of the myeloma stem cell.

3. Targeted Treatment based on Genetics and Epigenetics* of Myeloma • Understand the genetic basis of myeloma and use this information to design targeted treatments aimed at switching off the

relapse. We will utilize the knowledge we have gained about the clinical behavior and molecular subtypes of myeloma to design therapies that target the genetics underlying the disease process. We will also harness the immune system to target residual disease — cancerous cells that remain after treatment when the patient is in remission and that often cause relapse.

The impact of these advances will be assessed

genetic signals that lead to its development.

by novel disease-monitoring methods aimed

* Epigenetics refers to the biological mechanisms that

at decreasing the time needed to evaluate the

switch genes on and off in a stem cell. Epigeneticsbased treatments are based on programming cells in order to modify the on-off mechanisms.

4. Total Treatment Approaches to Curing Myeloma • Harness the immune system to overcome resistance to treatments.

• Target treatment to the molecular lesions that cause myeloma.

effectiveness of new therapeutic interventions.

For example, by using molecular diagnostic tests and functional imaging studies, we can determine if a given treatment is effective. If it is not working as desired, it can be quickly adapted to include different agents.

We will integrate data from next generation sequencing (high-speed technology that enables

• Reduce treatment toxicity.

in-depth study of genomics and molecular

• Modify regimens for frailer patient

biology) into our previous classification systems

populations.

in order to develop tests that can be used to direct specific therapies. We expect that our new

Overall Theme Moving Forward With the four basic paths described above

myeloma biology and its impact on the bone

as guiding principles, the overall theme for

marrow microenvironment, will lead to improved,

our strategy moving forward is continued

individualized treatment plans, minimize

therapeutic progress toward growth control and

treatment-related side effects, and increase

cure of myeloma. This will be accomplished by

patient survival.

leveraging the advances we have made during

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studies, through an increased understanding of

In short, we will improve cure rates in high-

the 26-year history of our Total Therapy program

risk myeloma by rapidly translating preclinical

to craft solutions to reverse the poor outcome of

science to innovative therapeutic intervention

high-risk myeloma.

at relapse and thereby improve the standard of

Our goal is to develop a “Precision Medicine”

care for newly diagnosed myeloma patients.

strategy for high-risk disease. To achieve this, we

Our research strategy is divided into five

will develop solutions to overcome the problem

specific projects that are supported by core

of intraclonal heterogeneity (diversity within the

services, including biostatistics, clinical trial

myeloma cells), which we have shown to be a

research coordination, and advanced DNA and

key mechanism leading to treatment failure and

RNA technologies. myeloma.uams

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Project 1, Strategies for Cure in Newly Diagnosed Multiple Myeloma, will implement a clinical trial utilizing single agent anti-CD38* monoclonal antibody for induction and

High-Risk Myeloma

consolidation/maintenance. We will integrate IMiD** drugs in combination with the antibody.

We will develop novel molecular endpoints and diagnostics for assessing effectiveness, stratifying

Targeted therapy

cases, and directing therapies.

Novel drugs

*CD38 is a surface protein that is expressed by most, if not all, multiple myeloma cells. Anti-CD38 monoclonal antibody is believed to induce tumor cell death through multiple immune-mediated mechanisms of action. **IMiD stands for immunomodulatory drug. IMiDs are a group of compounds that are analogues of thalidomide and have anti-angiogenic (countering blood vessel development) properties and anti-inflammatory effects.

Project 2, Developmental Therapeutics, will develop expanded natural killer cell and antibodybased combinations aimed at enhancing natural killer cell activity against residual cancer cells that remain after chemotherapy. Additionally, this project will aim to enhance the activity of natural killer cells on a long-term basis and increase our understanding of how resistance develops.

Project 3, Precision Medicine Strategies, will develop an “Umbrella Study� so that novel targeted drugs and combinations of drugs can be quickly evaluated in specific molecular subgroups of myeloma. The Umbrella Study will focus initially on targeting the RAS signaling pathway, which, when permanently activated due to a genetic mutation, drives the proliferation and survival of myeloma cells. Additionally, the Precision Medicine Strategies project will focus on developing biomarkers for targeting specific disease subgroups and a pipeline of agents for entry into the Umbrella Study.

Virotherapy

Immunotherapy

Umbrella studies are designed to test the impact of different drugs on different mutations in a single type of cancer.

Project 4, Targeting the Microenvironment for Growth Control, will investigate the properties of the bone marrow microenvironment cells and the molecular pathways that drive progression of high-risk myeloma cell clones within the microenvironment.

Project 5, The Genetics of High-Risk Myeloma, will characterize the driver genetics and epigenetics of high-risk myeloma and investigate how they can be therapeutically targeted. We will define the mutational basis of disease progression, resistance, and high risk.

The integrated approach of these projects within our research strategy will link clinical and preclinical work and provide a framework through which improvements in laboratory research can be rapidly translated to patient care. Our studies will lead to improved treatment allocation, will reduce treatment-related toxicities, and will increase survival.

myeloma.uams

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8

myeloma.uams

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Excellence Distilling

C

ommitment to excellence… focus on customers… ongoing improvement… ingenuity and

resourcefulness… treating others with dignity and respect… nimbly adapting to new developments.

These are values that help an organization perform at its

best and endure. They have guided Heaven Hill Distilleries throughout its 80-year history and have ensured its success.

America’s largest family-owned and operated distilled spirits producer, Heaven Hill Brands, based in Louisville, Kentucky, has grown beyond its traditional roots as a Bourbon distiller to become the country’s seventh largest overall distilled spirits producer with a portfolio of innovative and relative products.

Since Heaven Hill was founded in 1935, the Shapira family has been at the helm. Heaven Hill has always taken great pride in being family run. With its third generation of family management in place, the company’s unique position in the industry is assured well into the future.

Andy Shapira, member of that third generation, is committed to upholding Heaven Hill’s lauded excellence in the industry. He is also committed to ensuring that Heaven Hill does its part to enhance quality and enjoyment of life through philanthropic support.

Shapira and his family have exercised their profound belief in “giving back” by supporting the Myeloma Institute and its cutting-edge research. Here’s why…



distill (us) verb or chiefly British distil /di' stil/ to take the most important parts of something and put them in a different and usually improved form; to extract the essence of.

-Merriam-Webster Dictionary

myeloma.uams

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In 2013, Shapira visited his local emergency department with a bout

In fact, they had numerous Heaven Hill

of food poisoning. A CT scan of his

business connections here, all of whom

gut revealed abnormal spots on his

were eager to help if needed. They

bones, and blood work indicated

readily bonded with other patients and

myeloma – certainly not what he

caregivers, including some from the

expected from a hospital encounter

Middle East, Asia, and Mexico.

triggered by eating bad food. With the

with the people who clean the infusion

Shapira researched his options and

unit floor. Everyone knows what you are

was intrigued by the depth of research

going through,” he said.

the charge with new treatment options, and we want to help.”

continues to be in sustained, complete

oncologist confirmed the wisdom of his

remission. “I was so fortunate that I had

choice.

the resources to go to Little Rock for treatment. It’s important to go where

Rhee, M.D., Ph.D., at the Myeloma

you can get the best treatment, if

Institute, Shapira knew he was at

possible.”

a center that shared the values so

In the spirit of giving back and with

fundamental to Heaven Hill. Surrounded

the goal of doing their part to ensure

by compassionate experts, he was

continued excellence for other patients,

confident he was at the right place.

Shapira and his mother chose to make

Based on the nuances of his disease, he

a meaningful donation to the Myeloma

underwent two stem cell transplants as

Institute. “UAMS is leading the charge

part of his personalized care plan.

with new treatment options, and we

“The outcome was great, although I have to admit the treatment was

want to help,” he said.

“We are making steady progress in

difficult. But, that’s why I came to

our research on harnessing the immune

UAMS. I was young and wanted

system to fight off myeloma,” said

aggressive treatment,” he said.

van Rhee. “This exciting research has

Shapira had three young daughters at

10

The best silver lining of all: Andy

program at UAMS. His Louisville

After his first visit with Frits van

leading

“There is a real connection here, even

mindset of a thorough businessman,

and clinical excellence of the myeloma

“UAMS is

away from home and work remotely.

tremendous potential for improving

the time - the twins are now 11 and the

patient outcomes. Support from the

youngest is 7 – and he was determined

Shapira family helps make this possible.”

to fight hard to knock out the myeloma.

The family’s commitment to ongoing

His wife did solo parent duty at home

improvement and ingenuity guides

with the girls while his mother, Ellen,

their investment in programs of

took on the caregiver role in Little Rock.

excellence that are making a difference.

Shapira and his mother found a lot

The Myeloma Institute is exceedingly

of silver linings while in Little Rock. It

grateful to the Shapira Family for its

was an easy place to set up a home

strong vote of confidence.

myeloma.uams

edu

A Phase II Trial of a Novel Proteasome/IMiD

the combination of ixazomib, lenalidomide and

Combination, Ixazomib, Pomalidomide,

dexamethasone had a VGPR (very good partial

and Dexamethasone, in Relapsed Multiple

response rate) of over 60 percent in newly

Myeloma Patients

diagnosed myeloma patients, suggesting that

UARK 2015-03

the combination of an oral proteasome inhibitor

Principal Investigator: Faith Davies, M.D.

with an IMiD is an effective treatment modality.

ClinicalTrials.gov Identifier: NCT02578121

This single arm Phase II study is designed

The primary objective is to determine the efficacy of ixazomib when combined with pomalidomide and dexamethasone, in terms of overall response rate in patients with relapsed myeloma. Previous studies have shown that

A Randomized Phase II Trial to Evaluate Three Daratumumab Dose Schedules in Smoldering Myeloma

to build on that data in order to develop an effective oral regimen which is well-tolerated for patients with relapsed disease. The long-term aim is to develop a backbone regimen to which future novel targeted treatments can be added as part of a personalized medicine approach.

Secondary outcome measures include: • Percentage of participants who are minimal residual disease negative.

UARK 2015-13 Principal Investigator: Gareth Morgan, M.D., Ph.D. ClinicalTrials.gov Identifier: NCT02316106 The purpose of this study is to evaluate three daratumumab dose schedules in participants with smoldering myeloma.

It is a randomized, open-label (identity of assigned treatment will be known to participants and study staff), 3-arm (3 treatment groups), multicenter study of daratumumab in patients

• Percentage of participants who achieve a complete response or partial response.

• Median time of progression free survival.

• Percentage of participants with symptomatic myeloma.

• Overall survival rate. *The concept of patient-years is used in many clinical studies and statistical assessments of risk. It enables researchers to look at a population more generally, rather than trying to separate out and process data from each

with intermediate or high-risk smoldering

individual member of a group. To obtain the number,

myeloma.

researchers add together all of the years that patients in

Primary outcome measures include: • Percentage of participants who achieve a

a study were followed, and then divide those years by the event of interest.

complete response.

• Percentage of participants who have an adverse event per patient-year.* myeloma.uams

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Advancing Cure with CyTOF Technology

We invite interested donors to partner with us to advance myeloma cure by supporting our acquisition of the CyTOF instrumentation.

Based on our years of experience in the

determine the cellular subtypes of the immune

research and treatment of myeloma and related

system. We have been able to determine what

diseases, we are confident that personalized

makes cancerous myeloma cells different from

approaches to treatment hold the best promise

normal cells and use this information to design

for a cure. The ability to customize treatment

optimal treatments and stimulate the immune

demands comprehensive knowledge about

system to fight cancer.

the nuances of each individual’s disease. With

Fluorescence-activated cell sorting, or flow

CyTOF technology, we will be able to explore

cytometry, has been the standard technique for

cell populations and biological systems with

recognizing the cellular subtypes of the immune

unprecedented depth and take our outstanding

system for many years. However, this technique

treatment modalities to new levels of excellence

is limited by the number of fluorescent tags that

in the pursuit of superior outcomes for every

can be used to identify cells, and therefore not

patient.

all of the integral components of the immune system can be identified simultaneously.

Background Over the past decades, our understanding of myeloma stem cell biology and immunology

12

Typically, up to eight markers can be used in this type of cell sorting.

To combat this limitation, a new technology

has been greatly enhanced by improvements in

has been developed that can detect up

single cell analysis technologies that have made

to 35 markers at the same time, allowing

it possible to quantify the expression of multiple

a more detailed examination of the many

genes on the surface of individual cells and

cell types present in the bone marrow and myeloma.uams

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their interactions. The technology couples flow cytometry with time-of-flight mass spectrometry, and is known as CyTOF (Cytometry by Time of Flight). With CyTOF, many more of the immune cell subtypes can be identified simultaneously. This will allow us to be more precise with our treatments.

How mass cytometry works: Cells are stained in suspension with a customized panel of metal-conjugated antibodies directed against surface and intracellular protein targets.

High-purity metallic isotopes ensure minimal background from signal overlap or endogenous cellular components.

How can CyTOF translate to improved patient care?

• Our researchers will be able to study how different immune populations in the bone marrow interact with myeloma cells and influence tumor growth and survival.

• CyTOF can study the function of the immune system at a single cell level, enabling us to further develop immune

Inside Helios cells are individually atomized to release the metal ions. Ions derived from each stained cell are maintained in discrete clouds.

therapy treatment options.

• We will gain a better understanding of the features of the cells that cause myeloma and related diseases by identifying signaling pathways that we can then target with specific therapies for improved

Metal ions of interest are resolved by mass in the time-of-flight (TOF) chamber.

outcomes with minimal toxicities.

• CyTOF and its analytic tools will help us evaluate and interpret disease evolution in serial patient samples and response to specific therapies.

• We will be able to expand serial patient samples into larger groups of disease-

The time-resolved detector produces a mass

resistant cell populations and cell signaling

spectrum that represents the identity and quantity

pathways that predict the risk of relapse.

of each isotopic metal tag or a per-cell basis.

Quantitation of metal ions is predictable, linear and

Your Support

highy resolved.

Your support of CyTOF technology will help ensure that every patient receives optimized treatment for his/her disease.

Please contact Jennifer Gurley, Senior Director of Development, at JMGurley@uams.edu for more information.

myeloma.uams

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Courtesy of Fluidigm Corporation

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Immune Cells of the Bone Marrow — A Brief Primer Bone marrow is the spongy tissue inside our bones that produces blood cells — red blood cells, platelets, and white blood cells.

White blood cells help the body fight against infection. There are many different types of white blood cells, including lymphocytes, neutrophils, and monocytes.

They fight against invading bacteria, viruses or fungi to help destroy infection.

Three major types of lymphocytes play an important role in the immune system.

B-lymphocytes (B-cells) originate in the bone marrow.

They make proteins called antibodies, which attach onto the surface of infectioncausing microbes. Generally,

T-lymphocytes (T-cells) mature in the thymus, which is a small organ in the upper chest, just behind the sternum (breastbone). T-cells help B-cells make antibodies against invading bacteria, viruses or other microbes. Unlike B-cells, T-cells can produce chemicals that kill infected cells after binding to the antigen on the surface of the infected cell.

T regulatory cells suppress immune responses of other cells. This is an important “self-check” built into the immune system to prevent excessive reactions.

Natural killer (NK) cells are a type of lymphocyte that directly attacks cells which have been infected by a virus.

these are Y or T shaped. Each type of antibody reacts to different microbes by sticking to molecules, called antigens, which sit on the surface of the microbe. It is this antibody-antigen binding that triggers B-cells to grow and produce more antibodies, which fight infection.

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myeloma.uams

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Monoclonal Antibody Therapy in Multiple Myeloma: Where Do We Stand and Where Are We Going?

Abstract Multiple myeloma is a

monoclonal antibody therapy in multiple myeloma. A large

plasma cell malignancy

number of preclinical and

that is characterized by

clinical studies have been

refractory and relapsing

introduced successfully,

course of disease. Despite

demonstrating a safe and

the introduction of high-

efficient administration of

dose chemotherapy in

monoclonal antibodies in

combination with autologous

multiple myeloma. In particular,

covering immunology and

stem cell transplantation and

the application of monoclonal

immunotherapy)

innovative agents such as

antibodies in combination

2016 Mar; 8 (3): 367-84

proteasome inhibitors and

with immunomodulatory

immunomodulatory drugs,

drugs, proteasome inhibitors,

Primary Author:

achieving cure in multiple

corticosteroids or conventional

Sharmilan

myeloma is a challenging

chemotherapy seem to be

Thanendrarajan, M.D.,

endeavor. In the last couple

promising and will expand the

Assistant Professor

of years, enormous advances

treatment arsenal for patients

were made in implementing

with multiple myeloma.

A new publication in the journal Immunotherapy (monthly peer-reviewed journal

http://www.ncbi.nlm.nih.gov/pubmed/26888183 myeloma.uams

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15

Walker brings

Molecular Genetics Expertise to the Myeloma Institute

A

specialist in molecular immunology and molecular

genetics, Brian Walker, Ph.D., left his native United Kingdom (UK) in

“I started

October 2015 to join the Myeloma

my career

Institute as professor of medicine and

studying the immune system of chickens.”

director of research.

As a high school student in Scotland, Walker expected he would pursue a career in mathematics until “a good biology teacher changed all that.”

Following his newfound passion, he studied general biology for two years and then specialized in medical microbiology at the University of Edinburgh.

For Walker, the appeal of medical microbiology “was the combination of immunology and disease, the host response to infection.”

Walker earned a Ph.D. in molecular immunology from Imperial College at the University of London in 2000 and then took a post-doctoral fellowship in molecular genetics at the Institute for Animal Health, now the Pirbright Institute, in the UK. “I started my career studying the immune system of chickens,” he said.

The focus was on antigen processing as related to the recognition of foreign materials. Basically, a viral protein, or antigen, is chewed up inside the cell

16

and put onto the surface of the cell in order for the immune system to be able to recognize the infected cell and stimulate an immune response to fight off the viral disease. Chickens are particularly good models for this type of study because they have a simpler immune system.

Some strains of chickens afflicted with the virus fight it off and do just fine, while other strains develop cancerous tumors and die. Genetics clearly plays a role. So, the challenge myeloma.uams

edu

is to understand the molecular genetics and

classifying myeloma according to chromosomal

manipulate the system so that the appropriate

differences. He was correlating the DNA

response is stimulated to attack the cells that

changes with already established RNA

are infected.

classifications in order to identify the most

In 2004, Walker’s interest was piqued by

important genes in terms of disease activity.

another postdoctoral fellowship opportunity,

Investigation of B-cell receptor mechanisms

this time under Gareth Morgan, M.D., Ph.D., now

(myeloma is a malignancy of plasma cells, which

the director of the Myeloma Institute, who at the

are B-cells) is a continuing theme for Walker, as

time was conducting cutting-edge research on

B-cells were first discovered in chickens.

novel microarray analysis at the UK’s Institute of Cancer Research (ICR).

Morgan was analyzing gene expression from myeloma patients with the goal of submyeloma.uams

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Studies were conducted on 30-40 samples from newly-diagnosed patients across the UK as part of a clinical trial at the ICR. Utilizing DNA versus RNA for these studies had ď § 17

a distinct advantage. Because DNA degrades

different sequencing technologies that allow

more slowly than RNA, the lag time from

scientists to sequence DNA and RNA more

securing a sample to shipping it to the ICR to

quickly than older methods, and, as such, have

processing it did not compromise its integrity.

revolutionized the study of genomics and

The studies, with Walker as lead scientist,

molecular biology.) But, he missed the myeloma

enabled examination of the prognostic

work and was eager to join a high-volume,

importance of molecular abnormalities in

cutting-edge program.

myeloma. Detection of poor prognostic markers

Walker’s vision for future research directions

helps identify high-risk patients who require

at the Myeloma Institute includes integrating

more intensive treatment.

gene expression profiling with DNA molecular

Much of the data on myeloma genetics is

profiling as a means of developing personalized

based at the chromosomal level. Walker’s

treatments. This will ensure that patients receive

team at the ICR performed whole exome

the most effective therapy aimed at their unique

sequencing, a technique for sequencing all the

disease features.

protein-coding genes in a genome (full set of

Walker looks forward to securing

chromosomes) on several large datasets. This

sophisticated equipment, specifically a NextSeq

enabled them to correlate abnormalities with

machine, to support this integrated profiling

the identification of prognostically important

approach. The NextSeq can process targeted

mutations and investigate the subclonal

panels (versus the whole exome) with a very

structure of myeloma at the mutational level.

quick turnaround, ensuring that patients are

The information revealed that smoldering

placed on appropriate clinical trials and receive

myeloma is very similar to myeloma,

the most appropriate treatment as quickly as

while MGUS (monoclonal gammopathy of

possible. Additionally, the machine will enable

undermined significance) is a less complex

creation of a pipeline for automated analysis.

disease state. An understanding of the

As soon as funding for the machine is secured,

subclonal structure of myeloma is key

Walker and his team will be charting a new

to understanding and predicting the efficacy

course for individualized medicine for myeloma

of treatments.

patients.

During his 10 years at the ICR, Walker

Without missing a beat, Walker has adapted

developed high-level expertise in deciphering

quickly to his new workplace and is actively

and understanding the role of molecular

advancing the research excellence for which the

genetics in myeloma survival.

Myeloma Institute is known worldwide.

Following Morgan’s departure from the ICR

As far as adapting to life in the United States,

to assume leadership of the Myeloma Institute

and particularly in a rural southern state, Walker

in July 2014, Walker moved on to the Royal

is also making strides.

Marsden Hospital in London to work on next

“I have already tried Gus’ Fried Chicken, and

generation sequencing for solid tumors, such

I like it,” he said. “But I do miss the Cadbury

as gastrointestinal and breast tumors. (Next

Chocolate and Heinz Baked Beans that we get

generation sequencing, also known as high-

in the UK.”

throughput sequencing, refers to a number of

18

myeloma.uams

edu

Research Grant Awarded To Dr. Schinke

therapy-related myelodysplatic syndromes (t-MDS) and acute myeloid leukemia (t-AML), both of which are not uncommon secondary diseases in patients with myeloma who have undergone high-dose chemotherapy.

Previous studies have shown the existence of t-MDS/t-AML clones prior to high-dose chemotherapy.

However, the sample sizes were small, thereby limiting the investigation of the mutation landscape of the aberrant cells.

Carolina Schinke, M.D.,

research for young faculty

With the vast patient

assistant professor at the

investigators and new avenues

population and stored bone

Myeloma Institute, has been

of research for mature

marrow samples at the

awarded a 2016 UAMS Medical

investigators.

Myeloma Institute, there is a

Research Endowment Fund

Schinke’s research project

unique opportunity to study

is “Pre-Treatment mutational

hematopoietic stem cells

Grants from the Medical

landscape of hematopoietic

procured from a large number

Research Endowment Fund

stem cells in therapy related

of t-MDS/t-AML patients prior

provide pilot research funding

myelodysplastic syndromes

to their development of the

that has the potential to

and acute myeloid leukemia.”

secondary disease.

grant.

develop into extramurally

The goal of Schinke’s

This will yield important

funded, scientifically significant

research is to understand the

information on pathogenesis

research projects. Support

pathogenesis and influence

and clonal evolution in t-MDS/t-

is focused on new areas of

of cytotoxic treatment in

AML.

myeloma.uams

edu

19

Fighting Back to Good Health

T

he ability to get up after being knocked

player, he went to The Citadel (also known as

down and rise to new heights is an attribute

The Military College of South Carolina) on a

that can help shape our lives and help us cope

basketball scholarship. He continued to play

with life’s challenges.

baseball and, as would be expected at a military

Chuck Cordell knows first-hand the value of this attribute. When struck with adversity, he

Following graduation, a less rigorous pace led

faced it head on, drew from his inner core to

to a bit of weight gain, but it didn’t take Cordell

fight it off, and emerged even stronger in body

long to get back into the swing of things.

and mind.

Literally. He moved to Pinehurst, North Carolina,

Cordell has played sports since an early age. Always an avid baseball and basketball 20

college, was in top physical condition.

and started playing golf. That led to becoming involved with the development of 1,265 acres of myeloma.uams

edu

magnificent rolling hills that now includes the

for training had always eluded him. With his

Forest Creek Golf Club and its two nationally

newfound goal of encouraging other myeloma

ranked courses.

patients, he was driven.

Things were going well. Cordell had a great

The Ultra was held on the grounds of Forest

family, and he had his dream job, set in the

Creek, Cordell’s home turf. Starting at 6:00

natural beauty of Forest Creek.

a.m., and with 12 hours allotted for completing

At age 54, feeling like the picture of health,

the race, the day was long. Cordell had plenty

Cordell received a diagnosis of myeloma during

of time to see the beauty of the grounds in a

a routine check-up.

new light — the sun rising over the golf course,

After researching his options, he came to

steam rising from the lakes and ponds —

the Myeloma Institute, where he underwent

and to marvel at the busy chatter of wildlife

intensive treatment including two stem

throughout the day. At the critical 26.2 mile

cell transplants and four years of heavy

mark, his daughter Caroline joined him for

chemotherapy and other drug regimens.

the final 3 ½ mile lap, giving him the boost he

Not one to give in, Cordell was determined to beat the myeloma, which at one point left him

needed to finish the race.

The multiple benefits for Cordell of

barely able to walk up his driveway, and work

participating in the Ultra far outweighed the

his way back to physical fitness. In complete

toil and sweat.

remission from his disease, he started strength training and resumed his golf game. Cordell regained his top-notch physical condition, prompting his personal trainer to suggest that he enter an Ultra marathon.

What is an Ultra marathon? One could think of it as a regular marathon on steroids. Instead of the standard 26.2 miles, an Ultra is 31 miles (50K).

How did Cordell do it? He worked out and he worked out some more. With 15 months of consistent training under his belt, Cordell decided to tackle the Ultra and use it to encourage and inspire other myeloma patients.

He wanted to share the message that life is not over just because one is diagnosed with myeloma. And, he wanted to give patients hope, knowing that advances in treatment, like those pioneered at the Myeloma Institute, can lead to a cure and enriched lives.

Running a marathon had always been on Cordell’s bucket list, but, the impetus and time myeloma.uams

edu

• Proceeds from the race were designated for “The Patriot Foundation,” which supports families of wounded or deceased service personnel from Fort Bragg, North Carolina and Fort Campbell, Kentucky.

• He had the satisfaction of knowing he was running to encourage myeloma patients to embrace the joys of life.

• He and his son developed a special bond as they trained together.

• As a bonus, his golf game improved from so much strength training and improved flexibility!

Most of all, through Cordell’s experience with myeloma and fighting back to good health, he has gained a new appreciation for the importance of “stopping to smell the roses,” staying in good physical shape, and having the courage to set high goals, no matter the outcome.

21

Harold Dean counsels a patient after treatment.

Whole Patient

Supporting the “There is a strong connection between good emotional health and physical healing.”

22

A diagnosis of a cancer like myeloma can be devastating.

Fear of the unknown, uncertainty

coping. They know about resources for emotional support, as well as financial assistance. They provide a

about the future, and concerns

safe haven, where patients and family

about how everyone — patient and

members can open up and express

loved ones — will be affected can be

their concerns, and shed tears.

overwhelming.

While doctors and nurses can offer

Soon after the UAMS myeloma program started in 1989, the need for

encouragement and information

social workers was recognized. At that

about what to expect, social workers

time, the majority of patients came

can provide solace and help with

from other states and other countries,

myeloma.uams

edu

and they remained in Little Rock

• Providing information and education,

for extended periods of time. Many

and making sure that patients and

patients had lengthy hospital stays

their caregivers are connected to sources

before outpatient transplants, first

of education.

initiated at the Myeloma Institute, became the norm. Patients were far away from home and displaced from

• Counseling about resources, including financial and spiritual.

all of their regular support systems —

• Helping patients and caregivers cope.

family and friends, work colleagues,

“We assess where they are, knowing that they

spiritual communities. Use of the

are dealing with a huge life change that impacts

Internet as an informational resource

them and their families. We provide emotional

and for social interaction was just in

support and we connect them with online

its infancy. Cell phones were far from

sources of information and support groups,” he

commonplace.

said.

Even today, despite advanced

“Patients form their own support groups,

communication tools and almost

too. Some even go on vacations together,”

universally wireless Internet access,

Crabb added. “They often bond when they are

patients derive comfort and peace

undergoing treatment at the same time.”

of mind from in-person, one-on-one relationships.

Of the Myeloma Institute’s full-time

Many patients derive tremendous benefit from one-on-one counseling sessions. In those cases when extensive counseling is indicated, the

social work staff of three, Jennipher

social workers refer patients to psychologists or

Boone is dedicated to the 30-bed

psychiatrists.

inpatient unit, and Harold Dean and Justin Crabb focus primarily

A special focus on the inpatient unit is discharge planning — making sure that patients

on outpatient services. Dean and Crabb are

have appropriate resources and services to

two of only five social workers in Arkansas

function well when they are back home.

who are certified by the Board of Oncology

Earlier this year, Boone, Dean and Crabb

Social Work. Certification is based on rigorous

launched a series of educational/support

requirements related to work experience;

sessions that featured an array of topics such as

participation in research in oncology, cancer

nutrition and new drug therapies. They plan to

survivorship, or palliative care; leadership

gauge which subjects are of most interest and

participation in community organizations, such

continually expand the series accordingly.

as the Leukemia & Lymphoma Society; and serving as preceptor to master’s level social work students.

Dean, with more than 30 years as a social

Their overarching goal is to equip patients and their families with knowledge and coping skills.

“There is a strong connection between good emotional health and physical healing. We want

work professional, coordinates the services

to do everything we can to help ensure a good

provided by the team. He outlines the role of

outcome for patients at the Myeloma Institute,”

the Myeloma Institute social workers as:

Dean said.

myeloma.uams

edu

23

Non-Profit Organization US Postage

PAID

Little Rock, AR Permit No. 1973

4301 West Markham #816 Little Rock, AR 72205-7199

the scenes Tarun Garg, Ph.D. Dr. Garg earned a Ph.D. in Zoology from Banaras Hindu University in India and completed post-doctoral fellowships in Neurobiology and Developmental Sciences and Multiple Myeloma at the University of Arkansas for Medical Sciences. Dr. Garg’s research is focused on developing highly activated expanded natural killer (ENK) cell therapy for high-risk relapsed multiple myeloma. Dr. Garg’s team has generated ENK-resistant myeloma cell lines in the lab and is currently studying the different mechanisms of resistance by using gene expression profiling, phenotyping, quantitative proteomics, whole exome sequencing, and RNA-seq.

Ya-Wei Qiang, M.D., Ph.D. Dr. Qiang completed her medical education and Hematology/Oncology specialty training in China. She has a Ph.D. in Tumor and Molecular Pathology and was a post-doctoral fellow in Cellular and Molecular Biology at the National Cancer Institute. Dr. Qiang’s laboratory at the Myeloma Institute focuses on the Wnt signaling pathway in the pathogenesis of myeloma and identification of molecular targets in the tumor microenvironment that harbors myeloma cells that are resistant to chemotherapy.