Clinical Trial Supports Stem Cell Transplants to Treat RMS Patients with High Disease Activity

A newly concluded clinical trial gives scientific evidence of the benefits that a stem cell transplant holds for multiple sclerosis (MS) patients who fail to respond to medications — with researchers calling the procedure a reasonable option for those with high disease activity.

Five years after the treatment — high-dose immunosuppressive therapy followed by autologous hematopoietic cell transplant — further disease activity or disability progression was not evident in the majority of patients in the study, and some even showed improvements from earlier disability.

But the study, “High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS,” was small, and researchers say its findings need to be confirmed in further trials. The work was published in the journal Neurology.

The HALT-MS Phase 2 clinical trial (NCT00288626), conducted by the Immune Tolerance Network (ITN), recently ended after five years of observations. The study team, led by researchers from the National Institute of Allergy and Infectious Diseases (NIAID), had released data in 2014 describing outcomes at three years in 24 patients who received the cell transplants.

All had high levels of disease activity, with frequent relapses and advancing disability, despite medical treatment.

The study showed that at five years, 69 percent had no further relapses, disability progression, or evidence of new brain lesions. Notably, none of the patients were taking any MS medications after the transplant.

The median change in disability, assessed by the Expanded Disability Status Scale (EDSS), had decreased by 0.5 points.

“These extended findings suggest that one-time treatment with HDIT/HCT [high-dose immunosuppressive therapy/hematopoietic cell transplantation] may be substantially more effective than long-term treatment with the best available medications for people with a certain type of MS,” Anthony S. Fauci, MD, and director of NIAID, said in a press release.

“These encouraging results support the development of a large, randomized trial to directly compare HDIT/HCT to standard of care for this often-debilitating disease.”

In this type of HDIT/HCT transplant, doctors harvest the patient’s own blood-forming stem cells. But the procedure is not without risk. For the transplant to be successful, patients need to go through a harsh round of chemotherapy to wipe out their immune systems.

Many patients experienced severe side effects, including infections, linked to the treatment. During the trial, three patients died, but the deaths were determined not to have been caused by the treatment.

Both the treatment and side effects can be compared to other studies using the same transplant approach. The researchers reported that earlier studies have shown that 68 percent to 70 percent of patients have no further disease activity after a transplant, measured at intervals of three to six years. Deaths, however, have been linked to the treatment in other trials.

“Although further evaluation of the benefits and risks of HDIT/HCT is needed, these five-year results suggest the promise of this treatment for inducing long-term, sustained remissions of poor-prognosis relapsing-remitting MS,” said Richard Nash, MD, the study’s principal investigator with the Colorado Blood Cancer Institute and Presbyterian-St. Luke’s Hospital.

Although stem cell transplants for MS patients are available at many clinics, a lack of formal evidence as to their effectiveness has largely prevented clinicians from either recommending or ruling against them as a treatment option.

The researchers underscored that further studies are needed, particularly comparing stem cell transplants with currently recommended approaches. At the same time, however, they said that transplants are a reasonable option for patients with high disease activity despite treatment.

“If these findings are confirmed in larger studies, HDIT/HCT may become a potential therapeutic option for patients with active relapsing-remitting MS, particularly those who do not respond to existing therapies,” concluded Daniel Rotrosen, MD, director of NIAID’s Division of Allergy, Immunology, and Transplantation.

The NIAID is a branch of the National Institutes of Health.