WASHINGTON – Myeloablative autologous hematopoietic stem cell transplantation was superior to monthly intravenous cyclophosphamide in patients with severe scleroderma with internal organ involvement in the randomized, multicenter Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial.
At both 54 and 48 months, a comparison of global rank composite scores favored myeloablation followed by CD34+-selected autologous hematopoietic stem cell transplantation (HSCT) over 12 monthly pulses of 750 mg/m2 cyclophosphamide in the intention-to-treat population of 36 and 39 subjects with diffuse cutaneous systemic sclerosis and high-risk lung and/or renal involvement who were randomized to the groups, respectively (P = .013 at 54 months and P = .008 at 48 months). In subjects who actually underwent HSCT or received at least nine cyclophosphamide doses, the effect was even stronger (P = .004 at 54 months and P = .003 at 48 months), Keith M. Sullivan, MD, reported at the annual meeting of the American College of Rheumatology.
The global rank composite scores were derived based on a hierarchy of outcomes including – in rank order – death, event-free survival, forced vital capacity, scleroderma health assessment questionnaire score, and modified Rodnan skin score (mRSS); each patient was compared, based on the hierarchy, with every other patient in the study.
HSCT was superior overall and within each of the components of the score, Dr. Sullivan said.
The findings were supported by secondary analyses showing that at 54 months, event-free survival was 79% in the HSCT group vs. 50% in the cyclophosphamide group, and overall survival was 91% vs. 77% in the groups, respectively; the differences between the groups were statistically significant, said Dr. Sullivan of Duke University, Durham, N.C.
“In advanced scleroderma, that is a remarkable finding,” he said of the nearly 30-point difference in event-free survival rates between the groups.
Further, disease-modifying antirheumatic drugs were initiated by 54 months in 9% of the HSCT recipients vs. 44% of those in the cyclophosphamide group, he noted.
The rate of serious adverse events was similar in the two groups, although grade 3 or greater adverse events, including treatment-related cytopenias, were more common in the HSCT group, as was herpes zoster. Remarkably, most serious adverse events and adverse events occurred in the first 14 months, Dr. Sullivan noted.
Treatment-related mortality at 54 months was 3% in the HSCT group, and 0% in the cyclophosphamide group, he said.
Study subjects were adults aged 18-69 years with mean baseline modified Rodnan skin score of 30, mean baseline forced vital capacity of 74%, and mean diffusing capacity of the lung for carbon monoxide (DLCO) of 53% of predicted. All but two had lung involvement.
“So [there was] significant skin and pulmonary impairment,” he said.
There are, unquestionably, risks with transplant, but the SCOT findings support myeloablative autologous HSCT as a significant advance in the care of diffuse cutaneous systemic scleroderma with internal organ involvement, as this approach provided superior long-term outcomes, compared with 12 months of IV cyclophosphamide, he said, adding that the global rank composite score developed for this study was a useful measure of scleroderma outcomes.
“Therefore it would be prudent to consider early referral to the transplant center for consultation, which would allow patients, earlier in their disease – before the mRSS hit 30 and the DLCOs hit 50 – to make informed decisions,” he concluded.
The SCOT trial was funded by the National Institute of Allergy and Infectious Diseases. The authors reported having no disclosures.