New Treatment for Sickle Cell Disease Shows Promising Results in International Trial

Researchers at Vanderbilt University Medical Center (VUMC) are touting data from a multicenter, international Phase 2 clinical trial demonstrating a new treatment for sickle cell disease (SCD).

Treatment options include: Nonmyeloablative haploidentical bone marrow transplantation (BMT) with thiotepa and post-transplant cyclophosphamide (PTCy); Equivalent efficacy The treatment is one-fifth the cost of a myeloablative gene therapy option recently approved by the FDA, according to Michael DeBaun, MD, MPH, director of the Vanderbilt Meharry Sickle Cell Disease Research Center.

Results of the 10-year study were published June 20 in the Journal of the American Society of Hematology. bloodThe two-year overall survival rate was 94.1%, with no difference shown between children and adults.

DeVaughn and Adetola Kassim, MD, professor of medicine and clinical director of the Adult Stem Cell Transplant Program at VUMC, led the international trial, which enrolled 32 children and 38 adults from five countries.

The team developed state-of-the-art treatment protocols.

“We are introducing a new approach to treat SCD that is as safe and less expensive than recent FDA-approved myeloablative gene therapy and gene editing trials,” said Devaughn, vice chair for clinical research and professor of pediatrics at Vanderbilt University Monroe Carell Jr. Children's Hospital. “It is essential that physicians and families are aware of our study results so they can make decisions about the best individualized treatment options.”

“One of the most important advantages of our treatment approach is that most transplant centers in the U.S. and worldwide are so familiar with the now routine half-matched transplant protocols with PTCy that they could offer this life-sustaining treatment starting tomorrow.”

Until now, adults with SCD have been offered few treatment options due to the scarcity of fully matched donors and the fact that most adults with SCD can tolerate myeloablative treatment before transplantation.

Haploidentical transplant protocols require only a half match from the mother, father, sibling or even child and are a non-myeloablative and usually fertility-sparing approach.

In a recently completed clinical trial, 90 percent of potential participants had a donor, significantly improving access to the life-saving treatment, researchers said.

“The results also indicate that the treatment is well tolerated in older adults with SCD, who have been excluded from conventional treatment with hematopoietic stem cell transplantation due to the inherent toxicity of conventional treatment in a population with a severe disease burden,” said Kassim.

Other study results found that 96% of participants were no longer taking immunosuppressant medications one year after transplant. Overall two-year survival rates for children and adults were about 95%, similar to the results of most SCD treatment trials. All eight cases of graft failure (when the donor's cells do not continue to grow in the recipient) occurred in children, but the children's bone marrow recovered completely after transplant and did not require additional treatment.

Further research is being conducted to improve donor bone marrow transplantation in children. At the same time, for adults, no further refinement of the protocol is needed.

“We still need to understand the late health effects of all SCD treatment therapies. Ultimately, we believe knowing the late health effects of different types of treatment therapies will help families make informed decisions about which type of treatment they want.”

Michael DeVaughn, MD, MPH, director of the Vanderbilt Meharry Sickle Cell Disease Research Center

The second treatment, to be approved by the Food and Drug Administration in 2023, consists of myeloablative gene editing and gene therapy, costing between $2 million and $3 million each.

DeBohn cited the following as the biggest takeaways from this research:

• Haploidentical transplant protocols are routinely performed in most regions, so children and adults with SCD living in middle- and high-income countries have easy access to haploidentical protocols.
• Two-year cure rates and overall survival rates are comparable to or better than those seen in gene therapy and gene editing trials.

DeVaughn noted that he and Kassim served as two of four co-chairs of an NIH-funded multicenter trial in the National Institutes of Health (NIH)-funded Bone Marrow Transplant Clinical Trials Network (BMT-CTN 1507), which was presented at the 2023 American Society of Hematology meeting.

“The now completed NIH BMT-CTN 1507 trial is an offshoot of the Vanderbilt Consortium. In that trial, the two-year survival rate for 42 adults was nearly identical to the Vanderbilt Global Consortium results. The combined results of the two studies, which included 80 adults, show that adults who are cured of SCD have excellent two-year survival rates,” DeBaun said.

“We, the Vanderbilt consortium members and trial participants, have provided an additional therapeutic option for treatment to 90 percent of children and adults with SCD and demonstrated the realistic possibility of global expansion of SCD treatment wherever there are existing bone marrow transplant programs,” he said.