CLEVELAND — Autologous hematopoietic stem cell transplantation, which has recently emerged as a potentially effective option for select patients, likely represents the future of treating progressive diffuse cutaneous systemic sclerosis, according to Soumya Chatterjee, MD, from the Cleveland Clinic.
“Autologous hematopoietic stem cell transplantation — this probably is the way of the future,” Chatterjee told attendees at the Biologic Therapies Summit. “There were some uncontrolled studies that have been published, but more recently three randomized clinical trials have been conducted so far, and the results are out.”
These studies include the American Scleroderma Stem Cell versus Immune Suppression Trial (ASSIST), published in The Lancet in 2011; the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, published in 2014 in JAMA; and, most recently, the 2018 Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial, published in The New England Journal of Medicine.
Stem cell transplantation likely represents the future of treating progressive diffuse cutaneous systemic sclerosis, according to Chatterjee.
According to Chatterjee, all three trials compared autologous hematopoietic stem cell transplantation with monthly intravenous cyclophosphamide in patients with severe systemic sclerosis. All three demonstrated a benefit in the stem cell arms regarding their primary endpoints — clinical improvements in ASSIST, event-free survival in ASTIS and change in global rank composite score in SCOT.
However, the SCOT trial, which took more than 10 years to complete across 26 centers, provided the most promising data, Chatterjee said.
In that open-label, phase 2 trial, researchers randomly assigned 75 adults aged 18 to 69 years with severe scleroderma to receive either myeloablative autologous hematopoietic stem cell transplantation or cyclophosphamide. According to the researchers, stem cell transplantation demonstrated long-term benefits, including improved event-free and overall survival.
“The bottom line here is that the follow-up of these patients showed longer survival, or survival without any complications, with transplantation,” Chatterjee said. “There was also improvement in the skin score, improvement in the vital capacity, in diffusing capacity of the lungs for carbon monoxide, in the health assessment questionnaire and disability index, and also in the mental and physical component of SF-36.”
However, these benefits came at a cost of increased expected toxicity, the researchers noted. There was one treatment-related death in the 36-member stem cell arm, compared to zero in the cyclophosphamide group, during the 54-month follow-up.
However, this 2.8% treatment-related death rate among the stem cell group in the SCOT trial was lower than that of the ASTIS trial, In that trial, eight of 79 (10.1%) patients in the transplantation arm died vs. zero in the control group, through a median follow-up of 5.8 years.
No deaths were observed in the ASSIST trial.
“The mortality rate was dramatically lessened from the ASTIS trial to the SCOT trial, maybe because of methodology, maybe because of duration of follow-up, which was less,” Chatterjee said. “However, the mortality rate in the SCOT trial was only 2.8%, or 3%, which indicates that this might be a way to go if you really want to offer disease modifying therapy.” – by Jason Laday
Chatterjee S. Systemic sclerosis — advances in therapy. Presented at: Biologic Therapies Summit VIII; May 16-17, 2019; Cleveland, Ohio.
Disclosure: Chatterjee reports no relevant financial disclosures.