Top Takeaways from ASH: Hydroxyurea demonstrates noninferiority vs. transfusion for stroke prevention

Treatment with hydroxyurea for stroke prevention among children with sickle cell anemia appears to be a viable alternative to chronic transfusion therapy, according to results presented at the ASH Annual Meeting and Exposition.

Russell E. Ware, MD, PhD, director of the division of hematology at Cincinnati Children’s Hospital and professor in the department of pediatrics at the University of Cincinnati, and colleagues found that hydroxyurea therapy was noninferior to chronic transfusion therapy. The ability to use a pill, rather than chronic transfusion therapy, for stroke prevention in these patients is “really, really huge,” according to Venee Tubman, MD, a pediatric hematologist/oncologist at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

Venee Tubman

Tubman, along with Thomas Coates, MD, and Jeremie Estepp, MD, discussed the impact of these findings with Healio.com.

Benefits, challenges seen with both approaches

Transfusion therapy, which is instituted after the detection of abnormal transcranial Doppler (TCD) screening velocities, has greatly reduced the risk of stroke among children with sickle cell anemia, but is not without drawbacks.

“There are a lot of challenges associated with chronic transfusion therapy,” Estepp, of the department of hematology at St. Jude Children’s Research Hospital, said. “If you transfuse someone with blood chronically, they will inevitably become iron overloaded – and iron overload is its own problem that requires chelation therapy. It’s expensive, and it is a challenge to get people to adhere to therapy.”

Jeremie Estepp

The benefits of using hydroxyurea for stroke prevention in these patients include the elimination of both monthly transfusions and the dangers of iron overload, Coates said. He is the section head of hematology at Children’s Hospital Los Angeles.

Coates put the findings from Ware and colleagues into context, examining the danger of stroke in these children and the impact of an alternative to indefinite transfusions.

Thomas Coates

“The consequences of stroke are horrific. The child can be perfectly normal in the morning and neurologically devastated for the rest of his or her life in the evening,” he said. “The TWiTCH trial demonstrated that hydroxyurea was not inferior to transfusion for primary prevention of stroke in patients with high TCD velocity. This gives us a way to address the problem that, based on previous studies, all patients, including those who may not have ever had a stroke, are committed to lifelong transfusion. This means they don’t have to come in for transfusions every 3 weeks and eliminates the issues associated with iron overload.”

However, there are limitations and factors related to trial design that are important to remain aware of when considering the study’s impact.

“There are many, many factors that go into compliance. Some are social and related to family dynamics; some are personal. Some of them are developmental,” Tubman said. Positive results with hydroxyurea “really do depend on patients and families being highly adherent.”

Estepp pointed to the study design used by Ware and colleagues.

“There were very particular inclusion criteria,” he said. “You could not have had a previous stroke, you could not have high-grade vasculopathy and you could not have had a transient ischemic attack in the past.”

However, these issues do not override the positive impact of the results.

“It was a carefully done prospective study,” Coates said. “It’s given us important information.” – by Julia Ernst, MS

Reference:

Ware RE, et al. Abstract 3. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Disclosures: There was off-label use of hydroxyurea for children with sickle cell anemia in this study. Ware reports receiving research funding from Addmedica, Biomedics and Bristol Myers Squibb, serving as a consultant for Bayer Pharmaceuticals and serving on data safety and monitoring boards for Eli Lilly. Coates reports serving as a consultant for Agios Pharmaceuticals, ApoPharma, Celgene, Ionis Pharmaceuticals (formerly ISIS Pharmaceuticals) and Novartis and receiving research funding from Celgene. Estepp and Tubman report no relevant financial disclosures. Please see the full study for all other researchers’ relevant financial disclosures.