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
edu
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
8
Welcome to the
16
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
edu
3
The Myeloma Institute’s Approach for
Advancesand aCure
Dr. Frits van Rhee visits with a patient prior to his infusion.
4
myeloma.uams
edu
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
edu
5
• 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
6
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
edu
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
edu
7
8
myeloma.uams
edu
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
edu
9
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
edu
11
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
edu
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
edu
Courtesy of Fluidigm Corporation
13
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.
14
myeloma.uams
edu
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
edu
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
edu
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.