Dr. Gareth Morgan Takes Helm at Myeloma Institute
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A PUBLICATION OF THE UAMS MYELOMA INSTITUTE FOR RESEARCH AND THERAPY
SUMMER 2014
Dr. Gareth Morgan Takes Helm at Myeloma Institute
as different as one fingerprint is and Dr. Morgan, Arkansas Governor
from another. It’s critical to develop Mike Beebe provided $5 million from
technologies that can read this General Improvement Funds. In a
fingerprint, and to determine what is $3-for-every-$1 match, philanthropic
driving the disease in each individual contributions raised by UAMS provided
patient, so we can kill or normalize the another $15 million for a total of $20
behavior of the myeloma cells. There million, which is helping pay for the
isn’t a single treatment for myeloma construction of new laboratories and
but rather, there are many different, expansion of the institute’s research
personalized treatment strategies, one program.
of which is appropriate for a particular “As Governor, I am very pleased
individual patient. We envision to provide funding to support the
establishing a series of clinical trials Myeloma Institute and Dr. Morgan’s
investigating new treatments based research,” Governor Beebe said. “What
on each patient’s unique myeloma has been built at the institute by Dr.
fingerprint.” Barlogie is truly remarkable and has
enabled Arkansas to become a world
There isn’t a single
leader in the research and treatment of
Dr. Gareth Morgan multiple myeloma. With this funding
treatment for myeloma and Dr. Morgan’s guidance, I’m
but rather, there are many confident the UAMS Myeloma Institute
World-renowned multiple myeloma
researcher and clinician Gareth Morgan,
different, personalized will continue pushing forward to fulfill
its mission in innovative and dynamic
M.D., Ph.D., joined the Myeloma treatment strategies, ways.”
Institute as its new director on July 1. one of which is Morgan expects to align the
Dr. Morgan succeeds Dr. Bart Barlogie, appropriate for a particular expertise of the Myeloma Institute
founder of the UAMS myeloma individual patient. with other world-class research and
program and director since 1989, who treatment institutions around the
will remain at the institute to continue world, especially with the Myeloma
treating patients and conducting “Dr. Morgan and I can infuse the UK Research Centre at the Institute of
research. myeloma program with a forward- Cancer Research in London. UAMS’
“I am thrilled to be taking up this moving emphasis on utilizing research position as a leader for the treatment of
new post,” Morgan said. “I will build and technology to benefit patients,” myeloma will make it a central player in
on the excellent work done to date as Dr. Barlogie said. “By bringing together this global collaboration.
well as the institute’s reputation as the our collective experience, we are “At the UAMS Myeloma Institute
world leader in myeloma treatment to optimally poised to implement the I envision conducting focused clinical
develop innovative approaches for all latest scientific and treatment advances, studies investigating how to improve
myeloma patients and to characterize while maintaining a focus on each the current excellent clinical results
and cure high-risk myeloma. Myeloma individual patient.” obtained at the UAMS Myeloma
is different for each individual patient, In support of the Myeloma Institute
Continued on page 2
MYELOMA BRIEFING • SUMMER 2014 1
Dr. Gareth Morgan cont’d from page 1
Institute as well as investigating how bachelor of medicine in 1981 from the of Myeloma UK, the UK’s respected
such advances can be translated into Welsh National School of Medicine. patient organization, as well as a
wider populations by engaging in large Since 2003, he has served as a professor member of the Scientific Board of the
phase-three studies including patients of Hematology and director of the International Myeloma Foundation
both in the United Kingdom and Centre for Myeloma Research at the and Scientific Secretary for the UK
USA,” Morgan said. Royal Marsden NHS Foundation Trust Myeloma Forum. He is also a founding
Morgan received his doctorate and The Institute of Cancer Research in director of the European Myeloma
on the genetics of leukemia from the London, Europe’s largest comprehensive Network.
University of London in 1991 and his cancer institute. Morgan is a director
Tribute to a Grandmother
ie ,
D ear D r. B ar lo g I
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re se ar my
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ot he r’ s lif e w ay to o earl y an
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br ok
, sh e was
ng br av e f ig ht . A lo ng th e way
away af te r a lo d to m an y , an d m y he
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m an y , a f ri en
a ch ee rl ea de r to ili ng , was
M y g ra nd m a was alway s sm
an d in sp ir at io n. w on de rf ul hu m an be
in g . S he
si on at e an d a
ki nd an d com p as ti m e to g et he r. Thi s y ear
on
uc h du ri ng ou r
ta ug ht m e so m to do na te m on ey
to th e
ke d m y f ri en ds
m y bi rt hd ay I as of m y g ra nd m a. My g ra
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te in m em or y
My el om a In st i tu ou , an d I th an k y ou
fo r th e
th e w or ld of y
m ot he r th ou g ht r. P le as e ke ep do in g won
-
sp en d to g et he
y ears w e g ot to at no bo dy an d no fa
m ily w ill
dm y ho p e is th
de rf ul th in g s an
in th e f ut ur e.
ha ve to su f fe r
W i th g ra ti tu de ,
Ila na C oh en Ilana and her brother Adam with their grandparents,
Eunice and Alan Galsky, on a 2013 family vacation in
Institute.
for research at the Myeloma Hawaii.
ha s ra ise d m ore than $1,400
Ilan a
2 MYELOMA BRIEFING • SUMMER 2014
Total Therapy: A Historical Summary
Most every patient at the Myeloma Institute is familiar with with low-risk myeloma is basically a
continuation of Total Therapy 3, but
the term Total Therapy. It is often considered ubiquitous with
includes, following low-dose Melphalan,
treatment at the Myeloma Institute. Gene Expression Profiling analysis
in order to help unravel Melphalan’s
What is Total Therapy and patients enrolled in Total Therapy 2 are mechanism of action. For patients with
how has it progressed over still alive today. high-risk myeloma, representing an
Total Therapy 3, begun in estimated 15-20% of patients, Total
the years? 2003, combined a multi-drug regimen Therapy 5 aims to provide dose-dense
Total Therapy, pioneered by Dr. that included the use of Velcade (a as opposed to dose-intense treatment
Bart Barlogie, refers to our unique proteosome inhibitor, also known to eradicate the high-risk myeloma and
approach to myeloma treatment, which as bortezomib) in the induction, prevent relapse.
has formed the foundation for successful consolidation, and maintenance phases Total Therapy 6 is designed for
patient outcomes at the Myeloma of the trial. This was in line with the those patients who have been previously
Institute. It encompasses the concept “total’’ concept of applying all active treated but not transplanted. Again, we
of attacking myeloma on every front therapeutic agents with the intent of employ a dose-dense strategy in treating
at the outset of treatment and utilizing developing curative treatment. The the myeloma. Early results have shown
novel combinations of all therapeutic incorporation of Velcade resulted in the method to be highly effective in
agents and methods of treatment that superior response rates in comparison to low-risk patients. The time to achieve
have been shown to be effective against Total Therapy 2. In addition, patients best response was faster in high-risk
the disease. It has been the driving were classified as having low-risk or myeloma; however, the duration was
force behind our extensive research, high-risk disease based on genomic shorter, substantiating the importance
incorporating a series of clinical trials abnormalities, with outcomes differing of maintaining a best response rather
that span well over two decades. between the two groups. This newly- than depth of response in high-risk
Over the years, Total Therapy has discovered ability to more specifically myeloma.
evolved as patient outcomes have been identify disease characteristics served as The newest Total Therapy protocol
analyzed, new agents have become a launch pad, so to speak, for targeted, is TT5B. Instead of using Velcade,
available, and specific nuances of individualized treatments. as in TT5, TT5B uses Carfilzomib
myeloma biology have been identified. Indeed, our ultimate goal of investigationally upfront and
Total Therapy 1, launched developing the best tailored treatment throughout all treatment phases.
in 1989, introduced the use of tandem plan that will cure myeloma patients We have clearly observed enormous
transplants. This was a novel and unique based on the unique features of their success over the years with our Total
approach. Twenty percent of the 231 disease has driven the design of our Therapy Approach as described in our
patients enrolled in Total Therapy 1, newest set of trials in the Total Therapy numerous publications. Our continued
are still alive today, in some cases up to family. Total Therapy 4 for low-risk progress suggests that cure for myeloma
24 years since initial treatment. disease, Total Therapy 5 for high- is, in fact, real.
Total Therapy 2, initiated in risk disease, and Total Therapy 6 for
1998, introduced randomized use of previously treated but not transplanted
the controversial agent, Thalidomide. disease build on the successes of our
Excerpts from Myeloma
This was the first time that Thalidomide earlier applications of the Total Therapy Institute publication…
was used anywhere for the treatment of approach. Improvement in long-term
myeloma. Patients on Total Therapy 2 Total Therapy 4 and outcomes with successive Total Therapy
who received Thalidomide experienced Total Therapy 5, which began in trials for multiple myeloma: are patients
a median survival of 9 years. This was 2008, were among the first for multiple now being cured?
a major breakthrough in the realm myeloma or any other cancer to involve
Leukemia. 2013 Jan;27(1):226-32.
of myeloma treatment outcomes and risk-specific treatment plans based on PMID:22705990
set a new standard for treatment that the genetic makeup of individuals’ http://www.ncbi.nlm.nih.gov/
was adopted by many other centers. myeloma cancer cells prior to being pubmed/22705990
Approximately 40 percent of the 668 treated. Total Therapy 4 for patients Continued on page 4
MYELOMA BRIEFING • SUMMER 2014 3
Total Therapy cont’d from page 3
Abstract
Patient Support Fund
“The concept of applying all “Being a patient can involve a very long journey that
active therapeutic agents in Total can really drain your finances and take a toll on your very
Therapy (TT) clinical trials for being,” says Susan Speer, a Myeloma Institute patient
newly diagnosed multiple myeloma from Sugar Land, Texas. Deeply moved by stories of
was pursued with the intent of hardship she heard in the clinic waiting room, Susan
developing curative treatment… and her husband Richard established a fund that assists
overall survival, progression-free patients with demonstrated need while in Little Rock
survival and complete-response for treatment.
duration all improved with the Since 2008, the fund has assisted more than 400
transitions from TT1 to TT2 patients. You can help ensure that the fund remains strong
to TT3… a strategy using all Richard and Susan Speer and healthy to meet the needs of patients in the future.
myeloma-effective agents up-front
seems effective at preventing, in Donations of any size truly make a difference.
progressively larger patient cohorts • $25 buys 5 meals at the UAMS cafeteria
over time, the outgrowth of • $50 buys 5 nights at the UAMS Family Home
resistant tumor cells that account • $40 buys 1 gas card
for ongoing relapses.” Donations can be made via check as follows:
1) Make check payable to UAMS Auxiliary*
Discussion 2) Enter Patient Support Fund on the memo line
“We have demonstrated 3) Mail check to:
improvements in patient outcomes Myeloma Institute Development Division
with successive TT protocols, which 4301 West Markham #816
applied to most comparisons of Little Rock, AR 72205
overall survival, progression free
*The Speer Patient Support Fund resides in a distinct account within the UAMS Auxiliary, a non-profit
survival, complete response, and organization that provides assistance to UAMS patients and is a component of the UAMS Center for
time to progression. The transition Patients and Families.
from TT1 to TT2 introduced
more intensive induction therapy
before tandem transplantation and
consolidation chemotherapy after
transplantation; the experimental
25 Years of Curing Myeloma
arm of TT2 added thalidomide to
this regimen. The transition to TT3
brought the addition of thalidomide
and bortezomib for induction,
consolidation and maintenance
phases. The substantive This October marks the 25th anniversary
improvements in patient outcomes
were accounted for by reductions in
of the myeloma program at UAMS.
relapses, not only in the subset of Bart Barlogie established the myeloma program in 1989 and,
patients who achieved CR but also with his colleagues, built it into a world-renowned center for
in the overall patient population.” excellence in myeloma treatment and research. Through his
innovative approaches, Dr. Barlogie has fundamentally
changed the course of multiple myeloma. Dr. Barlogie will
continue to treat patients and conduct translational research
at the Myeloma Institute.
4 MYELOMA BRIEFING • SUMMER 2014
Drug Trial at the Myeloma Institute Led to First
FDA-Approved Treatment for Castleman’s Disease
Carl Guenther was once told he had
two years left to live. But a new drug
treatment study led by the Myeloma
Institute’s Dr. Frits van Rhee has
stretched that once-grim allotment into
nine years and counting.
Guenther was about 30 when he
noticed he sometimes felt unusually
tired. He sweated a little more than
normal, too, but he brushed off these
seemingly minor complaints. After his
first wife died from ovarian cancer in
late 2004, Guenther, an Ohio resident,
dismissed his night sweats and weight
loss as the after effects of stress and grief.
But when he awoke one morning in
June 2005 to discover the lymph nodes
near his neck swollen to the size of golf
balls, he knew something was wrong.
A biopsy showed he had a rare lymph Dr. Frits van Rhee stands next to a liquid nitrogen tissue bank containing the largest bank of
node disorder called Multicentric HIV-negative Castleman’s Disease patient samples in the world.
Castleman’s Disease. His Ohio
oncologist told him that even with enlarged lymph nodes. It also can affect common causes of death in patients
chemotherapy, he had two years left. lymphoid tissue of internal organs, with the disease.
Multicentric Castleman’s Disease causing the liver, spleen or other organs Guenther didn’t take the news
is a rare blood disorder in which to enlarge. Infections, multisystem about Castleman’s passively. The night
lymphocytes, a type of white blood organ failure and malignancies, after receiving his diagnosis, he started
cell, are over-produced, leading to including malignant lymphoma, are researching the disease and looking for
possible treatments. He learned that
a clinical trial of siltuximab, a new
drug for Castleman’s Disease, was just
beginning at the Myeloma Institute
under the direction of Frits van Rhee,
M.D., Ph.D., the nation’s foremost
Castleman’s expert.
He emailed van Rhee, director
of developmental and translational
medicine at the Myeloma Institute,
and was surprised to hear back from
him within 15 minutes. Just a few
weeks later, he became the third patient
to enroll in the clinical trial.
“Of all the places in the United States
for me to be involved in a clinical trial,
I never would have thought Arkansas,”
Guenther said. “We have the Ohio
Carl Guenther routinely came to the Myeloma Institute from Ohio to help pave the way for the State University Comprehensive
recently FDA-approved drug to treat his Castleman’s Disease. Continued on page 6
MYELOMA BRIEFING • SUMMER 2014 5
Castelman’s Disease cont’d from page 5
Cancer Center, which is a very good diligent compliance was a great asset in guys who have come down with me to
institution, but they couldn’t help developing Sylvant.” Arkansas from Ohio can’t keep up with
me.” Unless a cure is found some day, me,” he said. “I attribute that to the
The new drug worked very well for Guenther expects to continue receiving treatments. I haven’t felt this good for
him. He felt no side effects from the the treatments for the rest of his life. a long time, and I mean long before I
treatment, and his symptoms went “I’m doing so well that most of the was diagnosed.”
away. That alone would have been
enough to motivate him to make the
700-mile trip from home to Little
Rock for drug infusion every three
weeks, but the care and people at
UAMS made it even easier.
NEW CLINICAL TRIALS
“It’s been a very positive experience
at UAMS,” he said. “Every staff Total Therapy 5B (TT5B)
member, even the janitor who comes TT5B is the newest of the Total Therapy protocols. Unlike TT5, which
in while I’m getting treatment, they’re incorporates the use of Velcade, TT5B uses Carfilzomib upfront and throughout
all polite, friendly. People in Arkansas all treatment phases (tandem transplants, inter-therapy, maintenance and
are much friendlier than in Ohio. consolidation). Inter-therapy cycles have been reduced from two to one to
The nurses are fantastic. There’s not a minimize prolonged thrombocytopenia. Carfilzomib is currently approved as
lot of turnover and I’ve had the same a second line of therapy after relapse on Velcade. Carfilzomib is being used
nurses for years. That’s nice.” investigationally in TT5B. TT5B is a Phase II trial for high-risk myeloma.
In April the FDA approved the
A Phase 3 Multicenter Study Comparing Oral Proteasome
Inhibitor MLN9708* Plus Lenalidomide and Dexamethasone
“It’s been a very positive Versus Placebo Plus Lenalidomide and Dexamethasone in
experience at UAMS,” he said. Adult Patients With Newly Diagnosed Multiple Myeloma
“Every staff member, even the Primary Objective: To determine whether the addition of oral MLN9708 to
janitor who comes in while I’m lenalidomide and dexamethasone improves progression-free survival in patients
with newly-diagnosed multiple myeloma
getting treatment, they’re all
Eligibility: Adult patients with a confirmed diagnosis of symptomatic myeloma
polite, friendly.” who have not received previous myeloma treatment and who are not eligible for
transplant
drug, called Sylvant and developed A Phase 3 Multicenter, Safety and Efficacy Study of
by Janssen Biotech Inc., making it Dexamethasone Plus Oral Proteasome Inhibitor MLN9708*
the first FDA-approved treatment
or Physician’s Choice of Treatment Administered to
for Castleman’s. The European
Commission approved the drug in Patients With Relapsed or Refractory Systemic Light Chain
June. Amyloidosis.
“Carl’s case and others like it Primary Objective: To determine whether dexamethasone plus oral MLN9708
show what a serious need there is improves hematologic response and 2-year heart or kidney deterioration versus a
for treatment options for patients physician’s choice of a chemotherapy regimen as selected from the list of offered
with Multicentric Castleman’s treatment options in patients diagnosed with relapsed or refractory systemic
Disease,” Van Rhee said. “With light chain amyloidosis
the FDA approval of Sylvant, Eligibility: Adult patients with biopsy-proven systemic light chain amyloidosis
physicians have a long-awaited with relapsed or refractory disease
treatment option for a group of
* Manufactured by Takeda Pharmaceuticals Company, MLN9708 is an investigational proteasome
patients who have been suffering
inhibitor for the treatment of patients with myeloma and Amyloid Light-chain Amyloidosis. It is the
with this chronic and debilitating first oral proteasome inhibitor to enter Phase 3 clinical trials.
disease. Carl has been a great help
in getting us to this point. His
6 MYELOMA BRIEFING • SUMMER 2014Leading Clinician-Scientist Joins Donations for Research
Myeloma Institute Faculty are essential and greatly
Dr. Faith Davies, formerly
with the Institute of Cancer
appreciated.
Research in London, joined Visit myeloma.uams.edu and select “Giving.”
UAMS as Professor of
Medicine on July 1. She is the
director of the Phase I Clinical Interested in Planned Giving?
Trials Program for both the Visit: giftplanning.uams.edu
Myeloma Institute and the
Winthrop P. Rockefeller
Questions?
Cancer Institute. As such, Dr.
Davies will develop a program Contact Janet Aronson or Amanda Smith at
Faith Davies, M.D. focused on innovative targeted 501-526-2873.
molecular therapeutics. Dr.
Davies is recognized internationally for her interest in
novel therapeutics and her expertise in the treatment of
relapsed refractory disease.
Dr. Davies has had an extensive career in the United
Kingdom, with an emphasis on myeloma starting in
1996 at the University of Leeds. Her laboratory-based
studies investigated identification of genetic and biological
Her laboratory-based studies investigated
identification of genetic and biological prognostic
markers of disease outcome.
prognostic markers of disease outcome. Based on the
recognition that a number of the markers could be
potential therapeutic targets, Dr. Davies was awarded a
British Society of Haematology travelling fellowship at the
Dana Farber Cancer Institute in Boston.
New Publication from the
At the Institute of Cancer Research and Royal Marsden Myeloma Institute
Hospital in London, Dr. Davies’ laboratory work was
aimed at identifying biologically-based therapeutic The future of autologous stem cell transplantation in
targets in myeloma that are amenable to small molecule myeloma Blood, June 3, 2014 (Epub ahead of print), PMID
interventions and translating these laboratory findings 24894774
into the clinical arena with a focus on individualized
http://www.ncbi.nlm.nih.gov/pubmed/24894774
treatment. She initiated a drug discovery program to
identify molecules for clinical investigation. Abstract:
As scientific coordinator of two very large United Autologous stem cell transplantation (ASCT) has long been
Kingdom myeloma studies, Dr. Davies played an active considered front-line therapy for newly diagnosed myeloma
role in translational research involving 4,000 newly patients. This Spotlight examines the role of ASCT in the
diagnosed patients. Analysis of data collected led to the era of novel drugs and argues that ASCT should continue
ability to sub-group myeloma which in turn supports a to be considered for eligible patients. Combination of
personalized medicine approach. In a clinical capacity, novel drugs with ASCT in a sequential treatment approach
Dr. Davies developed a dedicated Hematology/Oncology can attain long-term survival and perhaps cure a subset of
clinical trial unit for Phase I, II and III clinical trials in patients. ASCT will likely remain an important platform to
myeloma, and managed the autologous and allogeneic develop curative strategies in the foreseeable future.
transplant program.
MYELOMA BRIEFING • SUMMER 2014 7Non-Profit
Organization
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Myeloma Institute Advisory Board The Myeloma Briefing is a publication of the Myeloma
Carol Ammon, Chair Louis Cella Institute for Research and Therapy, Gareth Morgan, MD,
Wilmington, Delaware St. Louis, Missouri PhD, Director.
Lucia Dougherty Ken Halliday
Miami, Florida San Antonio, Texas The Myeloma Briefing is mailed to patients, referring
Bob Kohler Gladys Monroy physicians, supporters and friends, and can be found on the
Fayetteville, Arkansas Palo Alto, California Myeloma Institute website at http://myeloma.uams.edu/
Dag Skattum William Webb news/newsletters.asp
London, England Nashville, Tennessee
EDITOR Janet Aronson
Michael Birnbaum Stuart Cobb
San Antonio, Texas Little Rock, Arkansas
DESIGN Laurie Shell
Stephen Engstrom Denny Holman
Little Rock, Arkansas Dallas, Texas
Myeloma Institute for Research and Therapy
Denis McDonald Jimmy Moses 4301 West Markham Street, #816
New Orleans, Louisiana Little Rock, Arkansas
Little Rock, AR 72205
Joseph Walker Donald Yanick
Dana Point, California Wilmington, Delaware
Telephone............. 501-526-2873
Fax........................ 501-526-2273
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