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The 57th American Society of Hematology (ASH) Annual Meeting & Exposition

New Hematology Drugs: Progress and Challenges Discussed at the 57th ASH Meeting

Surabhi Dangi-Garimella, PhD
An early session on the first day of the annual meeting and exposition of the American Society of Hematology, being held December 5-8, 2015, in Orlando, Florida, saw presentations on the promise of newly approved hematology/oncology agents, in addition to the challenges that clinicians face in treating patients with these drugs.
An early session on the first day of the annual meeting and exposition of the American Society of Hematology, being held December 5-8, 2015, in Orlando, Florida, saw presentations on the promise of newly approved hematology/oncology agents in addition to the challenges that clinicians face in treating patients with these drugs. Physicians with clinical experience using these agents discussed the appropriate population, dosing, side effects, and adverse events presented by the real-world use of the molecules.

Chaired by Mikkael A. Sekers, MD, MS, from the Cleveland Clinic, participants included Kenneth A. Bauer, MD, from the Beth Israel Deaconess Medical Center, Anjali S. Advani, MD, from the Leukemia Program at Cleveland Clinic, and Sagar Lonial, MD, Winship Cancer Institute, Emory University School of Medicine.

Idarucizumab 
The first presentation by Bauer introduced idarucizumab (Praxbind), a humanized monoclonal antibody indicated for patients with dabigatran (Pradaxa), for reversal of the anticoagulant effects of dabigatran. Developed by Boehringer Ingelheim Pharmaceuticals, idarucizumab is used in emergency surgery or urgent procedures and to protect against life-threatening bleeding. Preclinical studies have shown that idarucizumab protects patients from bleeding when treated with the direct oral anticoagulant (DOAC) dabigatran.

“Idarucizumab, a fully humanized antibody fragment, or Fab, has high affinity specifically for dabigatran and has shown no non-specific binding to other agents,” said Bauer, echoing results presented at the meeting of the American Heart Association last month.

Presenting updates from the REVERSE-AD or Reversal Effects of Idarucizumab on Active Dabigatran study, which led to the drug’s approval, Bauer said that the management of dabigatran-related major bleeding using reversal agents can prove challenging.

REVERSE-AD included 90 patients treated with idarucizumab, who were divided into 2 cohorts. Group A included 51 patients who had uncontrolled bleeding with dabigatran, while those in group B were 39 patients who needed emergency surgery or procedure following dabigatran treatment. The patients were administered 5 g intravenous idarucizumab, back-to back in 2 separate infusions over 0 to 15 minutes. Within minutes of administration, idarucizumab normalized either elevated dilute thrombin time (dTT) or elevated ecarin clotting time (ECT), the study reported.
“The primary endpoints of maximum percent reversal of anticoagulant effect of dabigatran, based on central-lab assessment of dTT or ECT within 4 hours of idarucizumab,” explained Bauer. “Secondary endpoints were cessation of bleeding in group A and hemostasis during procedure in group B.”

While dTT normalized in 98% of group A and 93% of group B patients, ECT normalized in 89% of group A and 88% of group B patients, Bauer showed.

“Safety issues are a concern with idarucizumab,” said Bauer, including some thrombotic events observed within 3 days and 4 events later on. While there were no cases of hypersensitivity, the trial saw 18 deaths, 9 in each group. “But deaths were primarily related with comorbidities that these very sick patients suffered from,” Bauer added

An ideal treatment strategy for the management of dabigatran complications, according to Bauer, includes:
  • Discontinue or hold dabigatran treatment
  • Supportive care (with IV fluids, packed RBCs)
  • Activated charcoal within 2 hours of treatment
  • Localization management of bleeding site
  • Administer idarucizumab
He then listed some challenges associated with using reversal agents with DOACs, including:
  • Insufficient data on whether supportive measures suffice or whether invasive procedures may be necessary
  • Quantitative assays for DOACs are not yet available
“For intracerebral bleeding, early presentation to a healthcare facility, prompt diagnosis, and prompt administration of an effective reversal agent is critical to improve outcomes,” Bauer concluded.



 
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