O'Neal Comprehensive Cancer Center Magazine Spring 2020 | Page 29

A BOLD MOVE
Four years in the making
Costa spent more than four years conceptualizing
the idea behind MASTER, which is an acronym for
the Monoclonal Antibody Sequential Therapy for
Deep Remission in Multiple Myeloma clinical trial. The
MASTER trial is testing a combination of immunotherapy
drugs, including carfilzomib and the monoclonal
antibody daratumumab, with the aim of definitively
eradicating multiple myeloma in patients.
“The paradigm in multiple myeloma is that it is an
incurable disease that you treat aggressively early on,
and then you are on maintenance therapy forever,”
Costa explained.
After their initial treatment, that is, patients stay on
therapy for the rest of their lives to prevent the cancer
from returning, but unfortunately, it almost invariably
does return.
With MASTER, “we intentionally increase the
therapy up front and specify it to the patient’s own
body characteristics. Then, if the disease becomes
undetectable, which could be the early signature of a
cure, we stop treatment and monitor.
“That is what patients want, after all – a treatment that
gives them the possibility of eliminating any trace of the
myeloma without having to be on therapy for the rest
of their lives,” Costa said when the trial was announced
in 2018. “It is a bold move, but bold moves are what our
patients deserve.”
Minimal residual disease
How can doctors know if that bold move worked for
a particular patient? The key element, Costa says, is
detecting the presence of cancer cells with a very high
degree of precision.
Using next-generation genetic sequencing technology,
which is up to 1,000 times more sensitive than the
traditional methods of evaluating treatment response,
physicians in the MASTER trial can detect cancer cells at
a level of one in 100,000. Patients in the trial who have
eliminated minimal residual disease discontinue therapy
but are monitored for relapse at the molecular level so
that the disease can be attacked as quickly as possible if
it returns.
This is one of the first trials in multiple myeloma to use
minimal residual disease as a key outcome and the
first to modify a patient’s therapy based on achieving
minimal residual disease eradication.
“If you have a coordinated effort and
motivated investigators, you can do
great things.”
— Luciano Costa, M.D., Ph.D.
Associate Professor of Medicine,
Division of Hematology & Oncology
Costa’s presentation of the MASTER trial results was one
of three oral presentations he made at ASH, including
another report on interim results from a Phase 1 trial.
Since Costa arrived at UAB in 2014, accruals in multiple
myeloma trials have risen sharply, to 85 patients enrolled
in trials in 2019 from zero in 2013.
“We really built a team approach, where we put
the patient at the center, and really understand the
population we serve,” Costa said. “Then we really beat
the bushes to try to get the right opportunities and
clinical trials for those patients.”
Expanding clinical trials
In 2019, Costa was named to direct the O’Neal
Comprehensive Cancer Center’s Clinical Trials Office,
which provides infrastructure to facilitate the more than
200 clinical trials ongoing across the O’Neal Cancer
Center. His goal, Costa says, is to extend the same
approach that has worked in multiple myeloma across
many different cancer types. That includes working with
groups that allow experienced investigators to mentor
physicians early in their careers and help them navigate
the barriers to successful trials. It also includes a focus
on “creating our own concepts” for trials in order to
foster innovative ideas from faculty.
“Our patients come to us with so much hope,” Costa said.
“There are many interfaces to cancer research, but clinical
trials are the most tangible to the people we serve. That’s
really where cancer patients get first-hand interaction
with the research being done here at UAB. There is
plenty of data, as well as my own personal experience, [to
support] that the most important factor for a successful
clinical trial accrual is the motivation of the investigator.”
Watch Dr. Luciano Costa explain the
preliminary outcomes of the MASTER trial:
go.uab.edu/mastertrial
UAB.EDU/CANCER
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