OncoLog, Volume 60, Number 3, March 2015 Page: 4
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Improved Maintenance Therapy Promotes IV
Patients' Quality of Life After Stem Cell TranBy Kathryn L. Hale
High-dose chemotherapy followed by autolo-
gous stem cell transplantation can prolong
survival for patients with multiple myeloma.
However, patients remain at a high risk of
relapse even after transplantation. Main-
tenance therapy can extend remission in
these patients, and clinical trials at The Uni-
versity of Texas MD Anderson Cancer Center
are exploring new maintenance regimens
to further improve patients' outcomes.Myeloma patients and their physi-
cians must weigh the possible benefit
of prolonged remission against the risk
of adverse effects from maintenance
therapy. "The challenge," said Jatin
Shah, M.D., an associate professor in
the Department of Lymphoma and
Myeloma, "is finding therapies that are
effective at maintaining remission and
at the same time are easy for patients
to take over a period of years, with a
simple regimen and few and mild side
effects. The goal is to help patients
continue therapy with minimal disrup-
tion of their everyday lives."
Lenalidomide maintenance
Low-dose lenalidomide is the most
common maintenance regimen for
myeloma patients. Two recent clinical
trials showed that low-dose (10 mg)
daily oral lenalidomide prolonged
remission by 18-24 months after stem
cell transplantation compared with
watchful waiting. Early data from one
of the studies suggested that this ther-
apy also prolongs survival.
To minimize adverse effects and
increase the tolerability of maintenance
therapy, lenalidomide has usually been
given alone. Nevertheless, minor effects
such as diarrhea, rash, and fatigue do
occur. By far the greatest concern is a
second primary cancer, which occurs in8%-9% of myeloma patients who re-
ceive lenalidomide maintenance thera-
py but in only 3%-4% of those who do
not receive it. "While this doubling of
risk still means second cancers occur in
only a minority of patients," Dr. Shah
said, "it is an important risk that pa-
tients have to be aware of."
Bortezomib and ixazomib
Although low-dose lenalidomide
maintenance therapy has been shown
to be effective and well tolerated, re-
searchers are looking for ways to further
prolong remission and survival after
transplantation while minimizing the
risk of a second cancer. The combina-
tion of lenalidomide with the protea-
some inhibitor bortezomib was shown
to be effective in patients with newly
diagnosed and relapsed myeloma. How-
ever, bortezomib can be given only as
an injection or infusion, so patients
would have to visit the clinic every
week or two for an indefinite period
if they were to receive the drug as
maintenance therapy.
In an effort to improve patient con-
venience and quality of life, researchers
at MD Anderson are currently testing
the second-generation proteasome in-
hibitor ixazomib (also called MLN9708)
-which is given orally-in combina-
tion with lenalidomide for myelomamaintenance therapy in a clinical trial.
"We think that this will be an effective
strategy in prolonging remission," said
Dr. Shah, the trial's principal investiga-
tor. "But we don't know how much
improvement we'll see or what the side
effects will be. That's the reason for the
trial."
Because the focus is on long-term
outcomes such as relapse and survival,
the investigators are still waiting for
results. "What we can say right now,"
Dr. Shah said, "is that we have not seen
any unusual or unexpected toxic effects
in the patients who have begun the
therapy. We're reassured by how well the
therapy is tolerated by most patients."
Dr. Shah said that the all-oral regi-
men allows patients to work full time,
travel, and take part in the activities
they enjoy. "They come to the cancer
center once a month, they get their pills,
and they continue to maintain a good
quality of life," Dr. Shah said. "We've
seen no limitations for the majority of
these patients. It's very encouraging to
see that patients are able to do every-
thing they want to do despite the thera-
py-and we hope that we're providing
not only increased time in remission but
also better quality time."
Maintenance therapy
research continues
Dr. Shah hopes that eventually
there will be a marker to identify which
patients need maintenance therapy and
which do not. "The question is not how
to identify patients who will respond to
maintenance therapy, since most do,
but rather how to identify patients who
will do well without the therapy and
thus can be spared the potential side
effects," he said. "One of the things
we're looking at is minimal residual dis-
ease. Patients who could be shown by
special tests to have no minimal resid-
ual disease at a deep molecular level,
signifying deep remission, might not
need maintenance therapy. I think
incorporating such a test is the next
major step."4 OncoLog March 2015
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University of Texas M.D. Anderson Cancer Center. OncoLog, Volume 60, Number 3, March 2015, periodical, March 2015; Houston, Texas. (https://texashistory.unt.edu/ark:/67531/metapth639488/m1/4/?q=%22Business%2C+Economics+and+Finance+-+Medicine%22: accessed July 9, 2024), University of North Texas Libraries, The Portal to Texas History, https://texashistory.unt.edu; crediting UNT Libraries Government Documents Department.