ASH Clinical News Hematology Pipeline Update: Drug Updates from the | Page 6

FEATURES

How Should Clinicians Be Using Newly Approved Drugs
in Practice?
In 2015, the U.S. Food and Drug Administration (FDA) approved several new therapies for the treatment of hematologic disorders – ranging from the first reversal agent for
a novel oral anticoagulant to multiple options for treating multiple myeloma (MM). But how should these new
agents be incorporated into clinical practice?
At the ASH annual meeting, several experts discussed the clinical applications of three of these newly approved agents in the
“Special Education Session on Newly Approved Drugs:”
• Blinatumomab – approved on December 3, 2014, for the
treatment of Philadelphia chromosome-negative relapsed or
refractory B-cell precursor acute lymphoblastic leukemia (ALL)
• Panobinostat – approved on February 23, 2015, for the
treatment of patients with MM
• Idarucizumab – approved on October 19, 2015, for the
reversal of the novel oral anticoagulant (NOAC) dabigatran
The session, chaired by ASH Clinical News Editor-in-Chief Mikkael A. Sekeres, MD, MS, director of the leukemia program at
Cleveland Clinic in Cleveland, Ohio, was adapted from ASH’s webinar series on newly approved drugs, which feature presentations
by clinicians with significant experience with these agents discussing the challenges of treating patients with these new drugs,
including identification of the appropriate population and dosing,
side effects and adverse events (AEs), and even off-label use.
Blinatumomab
Anjali S. Advani, MD, associate professor of medicine at Cleveland Clinic, discussed blinatumomab, a bi-specific anti-CD19/
CD3 antibody for the treatment of acute lymphocytic leukemia
(ALL) in adults – a clinical area with significant unmet need. “In
pediatric ALL, almost 90 percent of children are cured, yet in
adult patients with ALL, at three years only about 41 percent are
cured,” Dr. Advani noted. “Historically, our options have been
limited in this disease.”
In clinical trials, blinatumomab demonstrated high rates of
disease-free survival, in both newly diagnosed and relapsed/
refractory ALL.
Dr. Advani noted that “the drug has a short half-life, which
requires continuous infusion and patient compliance.” At $89,000
for one month of therapy, the cost of blinatumomab is also a major
concern. “Typically, before this treatment is started, we need to get
insurance approval to make sure that it will be covered,” she added.
“One of the challenges with blinatumomab is that it requires an
inpatient stay, followed by a transition to outpatient care,” Dr. Sekeres added. “This has logistically been very challenging for cancer
centers to institute.”
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Hematology Pipeline Update

Panobinostat
Sagar Lonial, MD, chief medical officer of the Winship Cancer
Institute at Emory University School of Medicine in Atlanta, Georgia, provided an overview of panobinostat, a histone deacetylase
inhibitor, which was approved (in combination with bortezomib
and dexamethasone) for the treatment of MM in patients who have
received at least two prior standard therapies.
Understanding the toxicities with the panobinostat-based
combination is essential to understanding how to use this regimen
in practice, Dr. Lonial said. Diarrhea and fatigue were the most
common AEs of this regimen in clinical trials, though, he noted
that the high rate of grade 3/4 diarrhea was the result of adding
bortezomib to the combination. “As we look to adding panobinostat
into clinical practice going forward, we need to look for potential
partner drugs that do not add to the risk of diarrhea, or modulate
the dosing schedule to reduce this risk,” Dr. Lonial stated. Among
the other available proteasome inhibitors, “carfilzomib appears to
have a better pattern of potential synergy with panobinostat, with
less overlapping gastrointestinal toxicity.”
“There are certain patient profiles [including patients with
rapidly progressive disease or who have short durations of response
to triplet-based induction the Ʌ