Stem Cell Transplant for Sickle Cell Disease More Cost-Effective Than Gene Therapy

Non-myeloablative haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a more cost-effective strategy compared with gene therapy for treating sickle cell disease (SCD), researchers found.

Their cost-effectiveness analysis demonstrated that while gene therapy provides more quality-adjusted life-years (QALYs) than non-myeloablative haploidentical allo-HSCT (22.1 vs 20.1), that comes at a much higher cost — $2.75 million versus $1.15 million, reported George Goshua, MD, of Yale University School of Medicine in New Haven, Connecticut, and colleagues in Blood.

The incremental net monetary benefit of transplantation was $1,403,000 versus gene therapy, while the incremental cost-effectiveness ratio for gene therapy was $818,000/QALY compared with transplantation.

A cost threshold analysis determined that based on results from two prospective phase II trials, the price of gene therapy in the U.S. would have to be reduced by 66% to 71% to be as cost-effective as non-myeloablative haploidentical allo-HSCT. Substantially greater reductions would be needed in lower-income countries.

Transplantation was also more cost-effective than standard of care (treatment with hydroxyurea, pain management, and blood transfusion), which accrued just 14.3 QALYs at a cost similar to that of transplantation.

“Our results indicate that to match the value proposition of non-myeloablative haploidentical allo-HSCT, the cost of gene therapy in the U.S. needs a significant discount,” wrote Goshua and colleagues.

“If you look at the quality-adjusted life-years … transplant does not beat gene therapy on expected quality-adjusted life expectancy,” Goshua told MedPage Today, adding that this was primarily due to incidence of graft-versus-host disease (GVHD) associated with transplant.

The difference in QALYs between gene therapy and transplant — about 2 years — “is relevant,” Goshua said. “Quality of life with non-myeloablative haploidentical allogeneic stem cell transplantation is much better, but still not better than gene therapy. It’s just that the expected costs accrued with gene therapy are still going to be very, very significant, to the point where it raises the question of who actually is going to be able to get it.”

The results of the study reinforce that “there are two curative-intent options [for SCD], and both of them need to be discussed with patients in light of their specific risks and benefits, and tailored to the specific values and preferences of the patient,” Goshua noted.

“Transplantation shouldn’t be discussed as a worst option,” he added. “It should be discussed as an equal option, especially for folks who may not be necessarily eligible to receive gene therapy, or it may not be offered to them, or may not be affordable to them.”

In explaining the rationale behind the study, Goshua and colleagues pointed out that even though gene therapy has been shown to achieve durable remissions in SCD, it currently employs myeloablative conditioning, and its rollout has been slow “due to cost, need for adequate organ function, as well as limitations related to manufacturing delays, apheresis feasibility, and accessibility.”

Meanwhile, over the last decade, the use of non-myeloablative regimens with haploidentical donors has been used with increasing success in SCD. This strategy involves reduced-intensity conditioning, making it less toxic than traditional transplant and better for older or medically frail patients, and requires only a half-matched donor instead of a full match, which significantly expands donor access.

This approach — supported by results from the prospective BMT CTN 1507 trial and an international learning collaborative phase II trial — as well as improved GVHD prophylaxis strategies, has “contributed to overall survival and event-free survival in adults approaching 95%, with improved rates of graft failure and [chronic] GVHD nearing 10%,” observed Goshua and colleagues.

“As far as we know, there has been no other study that has looked at the value of transplantation against gene therapy, and so we wanted to provide that to be as transparent as possible for stakeholders,” Goshua said.

He and his colleagues acknowledged the study had several limitations, including the fact that the long-term efficacy and safety of both non-myeloablative haploidentical allo-HSCT and gene therapy are still being evaluated, with current evidence derived from relatively small trials with time-limited follow-up.

They observed that the landscape for these treatments is evolving, and noted that the Centers for Medicare & Medicaid Services is implementing the Cell and Gene Therapy Access Model, with the objective of increasing the availability of cell and gene therapies and decreasing immediate costs through outcomes-based payment contracts.

Similar efforts are underway globally to develop and implement cost-effective curative-intent treatments for SCD, they said.

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