Highlights of Hope Spring/Summer 23

In addition to improving overall average
survival from five to 15 months, the
findings suggest the effectiveness of
combining medications that target both the
immunological and epigenetic drivers of
cancers.
The trial was led by Dr. Casey O’Connell
of the University of Southern California, in
collaboration with Dr. Maria Baer of the
University of Maryland, and Dr. Kirsten
Grønbaek of the University of Copenhagen
and Rigshospitalet — all members of the
VAI–SU2C Epigenetics Dream Team.
“We are thrilled that administering a
medicine to reawaken the immune system
may benefit a subgroup of patients with
MDS, as this class of drugs is not currently
approved for these patients,” O’Connell
said. “We are now exploring blood-based
markers that identify which patients are
most likely to respond in order to design a
more personalized treatment approach in a
subsequent trial.”
MDS is a type of cancer that occurs when
the bone marrow can no longer make
healthy blood cells. These sick cells either
die early or are identified as a threat by
the immune system and killed, leaving the
body without enough healthy blood cells to
properly function. About a third of people
with MDS can progress to a more severe
and tough-to-treat type of blood cancer
called acute myeloid leukemia.
Approximately half of people with
MDS respond when treated with a
type of epigenetic medication called a
hypomethylating agent, which works by
correcting errors in how the instructions in
DNA are used. Unfortunately, responses to
these agents are not long-lasting. There are
limited treatment options for people whose
MDS returns after their initial course of
treatment.
To address this, the investigators paired
a novel hypomethylating agent with a
type of immunotherapy called a PD-L1
inhibitor that helps the body identify and
attack cancer cells. Survival among treated
patients appears to be longer than what has
been previously reported for this patient
population; this study lays some groundwork
for future studies that pair epigenetic and
immunotherapies to treat cancer.
“As this trial indicates, combining cancer
therapies has the potential to improve
survival and make a real difference for
people with cancer by allowing us to target
multiple vulnerabilities in cancer at once.
These findings represent an important
proof-of-concept that should inform future
research toward the next generation of
cancer treatment,” said VAI Chief Scientific
Officer Dr. Peter A. Jones, who co-leads the
VAI–SU2C Epigenetics Dream Team with
Dr. Stephen B. Baylin of Johns Hopkins
University and VAI.
The trial is one of 14 launched by the VAI–
SU2C Epigenetics Dream Team since its
inception in 2014.
Read more at vai.org/mds-clinical-trial-results.
Research funding for this work was provided by Van Andel
Institute through the Van Andel Institute–Stand Up To Cancer
Epigenetics Dream Team. Stand Up To Cancer is a division of
the Entertainment Industry Foundation. The clinicialtrials.gov
identifier for this trial is: NCT02935361.
VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE | 11