A 12-year-old Black male presented to Kris Mahadeo, MD, MPH, cellular therapy specialist, with ongoing pain crises related to sickle cell disease (SCD). After a relatively controlled disease course during childhood, the patient’s symptoms worsened in adolescence, leading to frequent hospitalizations.
A common result of SCD is vaso-occlusion, which restricts blood flow to tissues and causes pain, swelling, and other complications. When vaso-occlusive events become more frequent and severe, pain crises become chronic and debilitating.
“After many years of being relatively symptom-free, this patient’s condition escalated quickly and became unrelenting. He spent nearly two years in the hospital, off and on, with severe episodes of pain. He lost time in school, the ability to participate in activities, and socialize like a typical teen,” explains Mahadeo.
The standard of care for chronic pain crises is a bone marrow transplant, but this was not an option as the patient did not have a match.
Question: What innovative treatment did Dr. Mahadeo offer to resolve this patient’s chronic pain and hospitalizations?
Answer: Mahadeo offered this patient a novel gene therapy that earned FDA approval in 2023, for which Duke was a clinical trial site. Duke was the first in the southeast U.S. to offer this treatment to patients. Gene therapy uses a patient’s stem cells, modifies them, and reinfuses them so the body can make hemoglobin with anti-sickling properties.
“We have two gene therapies with different mechanisms of action, but this patient was a great candidate for the gene-modification therapy lovotibeglogene autotemcel based on the fact he had been on hydroxyurea, had elevated H2, was having active pain crises, was over age 12, and had no history of stroke,” says Mahadeo.
Lovotibeglogene autotemcel therapy first involves removing blood-forming stem cells from the patient and re-engineering them to produce HbAT87Q, which functions like healthy hemoglobin A. The re-engineered cells are then infused back into the patient’s body to produce red blood cells with a lower risk of sickling and occlusion. The goal is to reduce pain and organ damage associated with SCD.
“It can be a long process,” says Mahadeo. “The first hurdle is to collect enough stem cells, which can take months.” But for this patient, all stem cells were collected in one cycle. Within a few months, his cells were manufactured with the gene therapy and sent back to Duke. He was admitted to start standard-of-care chemotherapy before the infusion.
After the infusion, patients typically stay in the hospital for four weeks to monitor side effects and blood counts. Mahadeo reports that in this case, the patient exceeded expectations. “He didn’t have common side effects like mucositis, which can affect eating, and his counts recovered quickly. He reported a significant decrease in pain almost immediately and was discharged in less than four weeks.”
The patient continued to report no pain and returned to normal activities. “This is a wonderful result,” says Mahadeo. Gene therapy mitigates the risk of graft versus host disease (GVHD) because it uses autologous cells. It’s a great alternative to transplant for some patients. “We’re seeing this therapy greatly reduce the effects of SCD and improve quality of life. We are following patients long-term and hope it also extends the length of life for our patients with SCD.”
To refer a patient, call 919-668-1100 or email ptct-referrals@duke.edu.