HSCT for Severe Autoimmune Diseases

Julie Gould

More recently, researchers presented the results of the SCOT (cyclophosphamide or transplantation) trial at the 2016 ACR/ARHP Annual Meeting. The results are currently pending publication. Keith Sullivan, MD, is principal investigator of the trial, which studied 75 patients randomized to either cyclophosphamide (750 mg/m2/mo) or myeloablation (800 cGy total body irradiation with lung and kidney shielding, 120 mg/kg cyclophosphamide and 90 mg/kg anti-thymocyte globulin), followed by CD34+selected autologous HSCT. The trial demonstrated superiority of the HSCT treatment on clinical outcomes, with patients receiving HSCT showing a significant reduction in the use of disease-modifying anti-rheumatic drugs.

Dr. Georges, one of the study collaborators, explains, “We now have three randomized clinical trials that demonstrate the superiority of transplant over conventional chemotherapy, with the transplant arm having a superior overall survival. This is convincing evidence that autologous hematopoietic stem cell transplant is effective therapy for systemic sclerosis.” He continues, “People at both meetings I attended said this was a practice-changing study, that this should really give courage to patients who have significant diffuse systemic sclerosis with declining pulmonary function and increasing skin scores despite other treatments.”

Experts generally agree that autologous HSCT is often able to induce sustained clinical remissions in people with lupus.

In terms of the risk/benefit ratio of HSCT for systemic sclerosis, Dr. Georges is encouraged by the fact that in the SCOT trial there were no transplant-related deaths within the first 100 days after transplant. (There were, however, two patients who later died from myelodysplastic syndrome, one at 15 months post-transplant and another 5.7 years post-transplant.) In contrast, 10% of patients in the HSCT arm of the ASTIS trial died from treatment complications within 100 days of transplant. “I think many rheumatologists were disappointed with this mortality outcome from ASTIS,” he notes.

Dr. Georges speculates the difference may have arisen from varying conditioning regimens between the studies. For the pretransplant regimen, the ASTIS trial used a higher dose of cyclophosphamide (200 mg/kg). In contrast, the SCOT trial used a lower dose (120 mg/kg). “What is interesting is that radiation plus cyclophosphamide at 120 mg/kg from the SCOT trial seemed to be better tolerated than the ASTIS regimen. The SCOT trial had fewer patients in the ICU, no patients with early transplant deaths and also an excellent disease response.”

Dr. Georges hopes treatment centers will begin making HSCT a standard treatment option for systemic sclerosis patients who meet specific criteria, not solely as part of clinical trials. This may also increase the number of patients receiving insurance approval for the procedure. He notes that the SCOT trial had trouble accruing patients because of lack of approval by insurance companies. “Over 200 patients tried to get into the study, but only about 75 patients ended up having insurance approval. That was frustrating for patients, physicians and researchers.”