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 onNewly 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.


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.”


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 therapy] that are best suited to panobinostat-based therapy rather than carfilzomib, and this is where the addition of panobinostat represents a significant step forward,” Dr. Lonial said.

Using genetic markers to predict patient response will also help with sequencing of the newly approved myeloma therapies, he added. “All of the new drugs coming out are going to need biomarkers to help us understand them, and that’s certainly a feature of ongoing trials.”


Lastly, Kenneth Bauer, MD, professor of medicine at Beth Israel Deaconess Medical Center in Boston, Massachusetts, discussed idarucizumab, a humanized monoclonal antibody fragment that is designed to reverse dabigatran’s anticoagulant effects when patients require emergency surgery or urgent procedures or are experiencing episodes of uncontrolled or life-threatening bleeding with dabigatran.

“These drugs have many characteristics that make them much more user-friendly than vitamin K antagonists like warfarin,” Dr. Bauer noted. “One of the issues that made physicians reluctant to prescribe these drugs over warfarin, though, was the fact that there were no specific reversal agents to manage bleeding associated with these oral anticoagulants.”

With the approval of idarucizumab, followed by dabigatran’s approval, based on results of the phase III REVERSE-AD trial, Dr. Bauer commented, “We no longer need to seriously consider prothrombin complex concentrates (PCCs), activated PCCs, or recombinant VIIa or to employ dialysis in the management of dabigatran-related bleeding,” he stated.

Still, there are many challenges in using reversal agents for major or life-threatening bleeding associated with this class of anticoagulants, such as the lack of qualitative assays for these agents – and that the assays that are available do not return results quickly. “Rapid point-of-care tests could be helpful in guiding management,” Dr. Bauer said. Also, given the fact that prompt diagnosis and administration of a reversal agent is the key to improving outcomes when life-threatening bleeding occurs. “Will smaller community hospitals stock these drugs, given the frequency of use and cost?”

Dr. Sekeres echoed these concerns in an interview with ASH Clinical News, “At a large institution like Cleveland Clinic, we are going to see these patients and we are going to stock the agent in our main hospital. But if you’re at a smaller institution, is it worth keeping this drug on the shelf when, eventually, it may expire and you’ll have to absorb the cost of that drug?”

Click here to watch our interviews with Dr. Sekeres and Dr. Lonial.