On Location
IOM WORKSHOP TACKLES IMMUNOTHERAPY
DEVELOPMENT, USE ISSUES
arlier this year, the Institute of Medicine’s (IOM’s) National Cancer Policy Forum (NCPF), the National Academies of Sciences, Engineering, and
Medicine, and the Health and Medicine Division (HMD) sponsored the
“Policy Issues in the Clinical Development and Use of Immunotherapy
for Cancer Treatment” workshop to discuss challenges in the creation and adoption of novel therapeutics – from designing clinical trials to managing patients’
expectations about treatments.
During the two-day event, oncologists, hematologists, pharmaceutical industry representatives, and regulatory officials shared insights on the state of
immunotherapy and presented strategies to improve the development process
and facilitate patient access.
“Many people might conclude that we’ve gone as far as
we can with cytotoxic chemotherapy, in part because of
the collateral damage that’s caused by the drugs that have
been used for the last 40 years to treat solid tumors and
hematologic malignancies,” said Richard Larson, MD,
professor of medicine at the Pritzker School of Medicine
in Chicago, and an NCPF member who attended on
behalf of ASH. “Immunotherapy offers a more targeted
approach and, perhaps, a more user-friendly, patientfriendly approach in terms of overcoming the immunological tolerance for malignancies.”
As the field of immunotherapy
advances with great alacrity and
enthusiasm for this treatment
modality grows, the cancer community must acknowledge that
older testing paradigms may not
apply, said Amy Abernethy, MD,
PhD, chief medical officer and
senior vice president of oncology
Amy Abernethy, MD, PhD
at Flatiron Health in New York
City and a member of the IOM workshop’s planning
committee.
People have a general understanding of how vaccines work, but there is a disconnect between established “mental models” of how a therapy works and
what immunotherapy potentially offers, she explained.
“Anti-cancer vaccines don’t really work the same way
as vaccines that immobilize the immune system – that’s
hard for people [to wrap] their heads around.”
Malcolm Brenner, MD, PhD,
professor at the Center for Gene
Therapy at Baylor College of Medicine in Houston, Texas, who also
served on the IOM workshop’s
planning committee and presented on adoptive T-cell transfer
said, “There’s always an educational lag when a field develops so
Malcolm Brenner, MD, PhD
quickly, but that’s changing,” with
immunotherapies making their way to the mainstream.
With chimeric antigen receptor (CAR)-modified
T-cell therapies, people are beginning to realize how
valuable T cells are in cancer therapy, Dr. Brenner said.
“In particular, with their ability to recognize internal antigens, traffic through multiple tissue planes, self-amplify
and recruit lots of other effector mechanisms – [they
reduce] the risk of resistance, and evolve with the tumor,”
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ASH Clinical News
making them very attractive therapeutic
candidates, he said.
Although there is excitement about
the potential of T cell-based immunotherapies, there remain a host of questions
about their application and of immunotherapy in general, he told ASH Clinical
News.
“We still don’t know how best to use
them: Which tumors should we use them
on? What should we use them with?
Should they be used with other immunomodulatory agents? Should they be used
with chemotherapy and radiation?” he
asked. “Designing the studies to look at all
that is going to be a major challenge.”
Clinical Trial Challenges
Evaluating immunotherapies in clinical
trials presents unique challenges, specifically with vaccines engineered to a
patient’s specific immune system.
In one presentation, Lisa Butterfield,
PhD, professor of medicine, surgery,
and immunology at the University of
Pittsburgh Cancer Institute in Pennsylvania, proposed integrating biomarkers
into clinical trials for immunotherapies
as a possible solution. These biomarkers
would help avoid toxicity and aid toxicity treatment, avoid ineffective therapies
for specific patients, and help researchers
understand immunotherapeutic mechanisms of action.
Given that some people are considered
“complete responders” to immunotherapy,
Dr. Butterfield wondered why clinicians
don’t have more useful biomarkers from
this cohort. “We need the right specimens
collected under standardized conditions.
Many trials bank only non-viable tumor
and blood samples and variably banked
specimens give noisy data that would
block the identification of biomarkers” she
said.
There’s also the issue of what assays
should be tested. Immune assays can be
costly, Dr. Butterfield noted, and testing
”[Clinicians have]
been taught to
take care of patients in a fairly
standard way.
But immunooncology is asking clinicians to
think differently.”
—AMY ABERNETHY, MD, PhD
small numbers won’t give robust, reproducible signals. Though there are remarkable new technologies available to conduct
immune profiling, there still is not a
robust set of data available that show how
effective they are in identifying patients.
Development of immunotherapy
biomarkers is limited not by technology,
according to Dr. Butterfield, but by diminished funding and protocols. For example,
she said, the National Cancer Institute’s
(NCI’s) Cancer Therapy Evaluation Program (CTEP) won’t allow exploratory biomarker inclusion in protocols and won’t
bank specimens for undefined exploration
of biomarkers; they want only integrated
or integral biomarkers.
“For immunotherapy biomarkers,
there are no integral biomarkers yet, they
are all exploratory,” Dr. Butterfield stated.
“This is a hurdle in the multi-institutional
trial setting.”
Historically, Dr. Abernethy explained,
clinicians have been attacking the tumor
head on but are now being asked to
May 2016