Stem Cell Transplant Benefits in People with Severe Systemic Disease Can Be Long-lasting, Trial Extension Data Show

Stem cell transplant confers superior and long-lasting clinical benefits compared to conventional treatment with Cytoxan cyclophosphamide in people with severe systemic scleroderma, including better functional ability and disease control, and prolonged survival, long-term extension data from a Phase 2/3 clinical trial show.

The study, “Myeloablative Autologous Hematopoietic Stem Cell Transplantation for Severe Scleroderma: Long-Term Outcomes 6-11 Years after Entry on a Randomized Study Comparing Transplantation and Cyclophosphamide” was presented at the 2018 American College of Rheumatology (ACR)/Association of Reproductive Health Professionals (ARHP) ARHP annual meeting that ended on Oct. 24 in Chicago.

In the Phase 2/3 SCOT trial (NCT00114530), researchers compared the potential benefits of stem cell transplant with those of high-dose monthly Cytoxan in treating scleroderma. AT ARHP, they reported on clinical outcomes six to eleven years after the trial’s launch. 

The study included 75 adult patients (ages 18-69) with severe scleroderma who were randomly assigned to either receive an autologous hematopoietic stem cell transplant (HSCT) or one year of monthly infusions of Cytoxan. All had the internal organ involvement that is systemic scleroderma, and 97% showed lung involvement.

Patients in the HSCT group were first treated with total-body irradiation to destroy their  immune cells (myeloablation), followed by chemotherapy and reconstitution of the immune system with stem cells previously collected from the patient’s blood.

Previous results, covering four and a half years of follow-up, showed that a 79% of transplant patients had no signs of disease progression, compared to 47% in Cytoxan-treated patients. HSCT also significantly increased survival, with an 86% overall survival rate in these patients compared to 51% in those given Cytoxan after 72 months.

An extension study, which monitored 25 HSCT and 18 Cytoxan trial participants for at least six and up to 11 years shows that the clinical benefits of HSCT are durable.

Out of the initial 75 participants, seven treated with HSCT and 18 treated with Cytoxan have died.

At the 11-year mark, the estimated overall survival was 80% for those given a stem cell transplant, and 52% for those treated with Cytoxan.

Compared with Cytoxan treatment, physical functioning and weight gain improved after a transplant. Stem cell-treated patients also showed better performance in daily life measures:  their employment rates, and physical and social functioning tended to be higher, but were not statistically different .

A huge majority, 92%, of HSCT patients were able to stop using disease modifying anti-rheumatic drugs (DMARDs), compared to 61% in those treated with Cytoxan, demonstrating more disease control in transplant survivors.

Two patients in the HSCT group developed organ failure versus six in the Cytoxan group.

“This study now extends follow-up of the study to six to 11 years after randomization. To show that the scleroderma has improved after transplant and results are durable for a decade off immunosuppressive drugs is a truly exciting development and a new approach to definitive treatment of autoimmune disease,” Keith M. Sullivan, MD, a professor of medicine at Duke University School of Medicine, and the study’s lead author, said in a news release.

The research team’s next goal “is to understand why it works.” According to Sullivan, it will be fundamental to demonstrate “that after hematopoietic stem cell transplantation, but not after conventional cyclophosphamide treatment, the genomic signatures of scleroderma resolve.”