Some 90% of patients with relapsing-remitting multiple sclerosis had no clinical relapses or signs of progression 3 years after receiving high-dose immunosuppression followed by autologous hematopoietic stem-cell transplant, researchers reported.
Interim results from 25 participants in the closely watched HALT-MS trial yielded a progression-free survival rate of 90.9% (95% CI 73.7%-97.1%) and a relapse-free survival rate of 86.3% (95% CIO 68.1%-94.5%), according to Richard A. Nash, MD, of the Colorado Blood Institute in Denver, and colleagues.
Most serious adverse events occurred within the first month after starting the myeloablative regimen, but nine patients experienced grade 3 events and one suffered a grade 4 event after year two of the study, Nash and colleagues reported online in JAMA Neurology. Another patient died during study year three from MS progression-related causes, they noted.
These late adverse effects led two independent experts, writing an accompanying editorial, to caution that hematopoietic stem-cell transplant remained unproven as an MS treatment.
“The jury is still out regarding the appropriateness and indications of HCT [hematopoietic cell transplant] for MS,” wrote M. Mateo Paz Soldan, MD, PhD, of the University of Utah in Salt Lake City, and Brian G.Weinshenker, MD, of the Mayo Clinic in Rochester, Minn.
In addition to their concerns about the treatment’s safety, the editorialists also questioned the extent to which the desired “immune reset” had actually been achieved, given that new and/or enlarging brain lesions continued to develop and clinical relapses occurred in some patients more than 3 years post-transplant.
“This study raises concern that those endpoints [freedom from clinical or radiological relapse] have not been adequately achieved,” Paz Soldan and Weinshenker wrote.
But Nash and colleagues portrayed the results as a win for HCT, albeit with caveats about the study duration so far and the need for additional confirmatory trials. The study did not have a control group.
Study Details
The investigators noted that HCT has been tested in MS before, with ambiguous results, probably because patients tended to have advanced disease and therefore continued to show functional declines related to non-inflammatory neurodegeneration. HCT is not regenerative, but rather is intended to terminate the immunologically mediated demyelination that sets the stage for, but is not directly causative of the subsequent neuronal and functional loss.