By Stacey Butterfield
In the past few years, the number of drugs approved by the FDA for sickle cell disease has quadrupled. But that’s still not saying much, according to Sophie M. Lanzkron, MD, professor of medicine and oncology and director of the Sickle Cell Center for Adults at Johns Hopkins in Baltimore.
“This was the first molecular disease described in man, and now we only have four therapies that are approved, so we’re still behind where we should be in treating this disease,” says Dr. Lanzkron during her Internal Medicine Meeting 2021: Virtual Experience session on sickle cell disease, available Thursday at 1:45 p.m.
She reviews all four approved drugs during her talk, starting with the old standby, hydroxyurea, approved in 1998. Successful hydroxyurea therapy requires avoiding a number of common pitfalls, which Dr. Lanzkron reviews.
For one, don’t assume that patients who already have fairly high fetal hemoglobin levels don’t need it. “Patients who have fetal hemoglobin levels that are high—if they meet the clinical criteria for going on hydroxyurea, so having crises, symptomatic anemia, acute chest syndrome—I will start them on hydroxyurea,” she said.
In some cases, it’s the patient who doesn’t want to take hydroxyurea, due to concerns about toxicity. “This takes time and trust with patients to talk to them about the issues,” said Dr. Lanzkron. “There actually is very little toxicity described in the sickle cell population with hydroxyurea.” Tools from the American Society of Hematology, available online at www.hematology.org, can help with these conversations, she noted.
“Another mistake I see is failing to try and titrate the dose to the maximally tolerated dose,” which is a neutrophil count between 2,000 to 4,000 per microliter and reticulocyte and platelet counts of at least 90,000 per microliter, she said. Too short a trial of hydroxyurea is also a common problem. “Patients and providers should be aware that it could take three to six months to see an effect,” said Dr. Lanzkron.
Almost 20 years after the approval of hydroxyurea for sickle cell, L-glutamine joined the armamentarium in 2017. Its mechanism of action in sickle cell disease is not exactly clear, said Dr. Lanzkron. However, a trial found fewer pain crises and hospitalizations among patients randomized to the drug.
In 2019 came crizanlizumab, a humanized monoclonal antibody that binds to P-selectin and blocks its interaction with its ligand. The final new option is voxelotor, a polymerization inhibitor that reversibly binds to hemoglobin to increase its oxygen affinity.
During the session, Dr. Lanzkron reviews the pros and cons of these various treatment options, noting that cost is a major issue for all the newer drugs. She also offers her own strategies for choosing which therapy to prescribe and adds a few tidbits on dealing with the chronic pain that frequently affects patients with sickle cell disease.
Finally, she offers some good news. After a very long wait for advances in the field, everyone treating sickle cell disease should have more options in the near future. “It's really an exciting time in sickle cell disease. We have a number of new therapies, and there are about 40 new agents in the pipeline, which is really great,” said Dr. Lanzkron. ■