Stem Cell Transplant Induces Long-term MS Remission: HALT-MS 5-Year Data Published

Deborah Brauser

February 16, 2017

High-dose immunosuppressive therapy (HDIT) plus autologous hematopoietic cell transplantation (HCT) can induce long-term remission in multiple sclerosis (MS), new data from the open-label, phase 2 HALT-MS trial show.

In the study of 24 patients with relapsing-remitting MS who underwent HDIT/HCT, 69% had survival without disability progression, new brain lesions on MRI, or a relapse of MS symptoms (the trial's combined primary endpoint) 5 years after treatment.

In addition, the progression-free survival rate was 91% and the clinical relapse-free survival rate was 87%.

Interestingly, these outcomes were achieved without any maintenance on MS medications.

"The results are very good and show what could be a better way of controlling the process of this disease," principal investigator Richard A. Nash, MD, director of the transplant program at the Colorado Blood Cancer Institute in Denver, told Medscape Medical News.

Dr Richard A. Nash

But because of the study's small sample size and design, he noted that "we're taking a wait-and-see approach" until a randomized trial can be conducted in this patient population.

Initial 5-year findings from the HALT-MS trial were presented at last year's Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting. The new, fuller results were published online February 1 in Neurology.

3-, 4-, and 5-Year Results

HALT-MS was created to assess, over 5 years, patients with MS who underwent HDIT/HCT. Although 25 patients aged 18 to 60 years (mean age, 37 years; 68% women) went through evaluation, 1 did not undergo the procedure.

At baseline, all had scores of 3.0 to 5.5 on the Expanded Disability Status Scale (EDS), had had MS for less than 15 years (mean, 4.9 years), and had at least 2 clinical relapses during the previous 18 months while taking disease-modifying therapy.

The participants underwent brain MRI at baseline, at 2 and 6 months after transplant, and then annually for up to 5 years. The mean follow-up was 62 months.

Three-year interim results were published online in 2014 in JAMA Neurology and showed that 78.4% of the participants had event-free survival (EFS). In addition, 90.9% and 86.3% had EDSS progression-free and clinical relapse-free survival, respectively.

At 4 years, the EFS probability was 73.8% (90% confidence interval [CI], 55.0% - 85.7%). And at 5 years, EFS survival was 69.2% (90% CI, 50.2% - 82.1%).

"Of 24 participants transplanted, 7 did not maintain EFS by close of follow-up…by an increase in EDSS > 0.5 (n =2), clinical relapse (n = 3), or development of new MRI lesions (n = 2)," report the investigators.

Table. Other Survival Analyses at 5 Years

Outcome Rate (90% CI) (%)
Progression-free survival 91.3 (74.7 - 97.2)
Clinical relapse-free survival 86.9 (69.5 - 94.7)
MRI activity-free survival 86.3 (68.1 - 94.5)
Overall survival 86.3 (68.3 - 94.5)


In all participants, including those who did not maintain EFS, relapse rates were reduced after the procedure compared with before treatment.

In patients who completed the study, EDSS score was significantly improved between baseline and 5 years after transplant (median change, –0.50; P = .001).

Also at the 5-year time-point, T2 lesion volume was significantly decreased (P < .001). Although overall brain volume decreased between baseline and year 5, it did not change significantly between years 3 and 5.

As for adverse events (AEs), "there were no significant late neurologic" events related to treatment.

And "AEs to 3 years…were consistent with toxic effects associated with HDIT/HCT, including predominantly cytopenias and infections," write the investigators.

Although there were 3 deaths (at 2.5, 3.5, and 4.5 years after treatment), none were attributed to the transplant.

Overall, the outcomes "are highly promising, as compared to non-HCT treatments," write the researchers.

"HDIT/HCT may present a potential therapeutic option for patients with [relapsing-remitting MS] who fail conventional immunotherapy."

However, they note that bigger and prospective trials comparing HDIT/HCT to other approaches are needed.

"Not for Everybody"

When initial 5-year results from HALT-MS were presented at last year's CMSC meeting, as reported by Medscape Medical News, co-investigator James Bowen, MD, from the Swedish Hospital Medical Center in Seattle, Washington, reiterated that the treatment should be targeted to a specific patient group.

"It's not for everybody," said Dr Bowen at the time. He added that it's most appropriate for those "with extremely aggressive disease."

Dr Nash reported that a randomized clinical trial, sponsored by the Immune Tolerance Network, is now in the planning stages and hopes to enroll more than 100 patients. These participants "will already have had some loss of neurological function and ongoing relapses and will have failed therapy."

When asked about treatment risks, Dr Nash said "whenever you drop a patient's blood counts, there's a risk of infections."

"And after transplantation, for patients with multiple sclerosis, there is a risk for mortality associated with this procedure. And that mortality may be 1% or 2%," he said. "So that's certainly something that should be kept in mind by any patient thinking of a transplant procedure."

Still, he noted cautious optimism with the treatment.

"I think there's a reasonable amount of excitement that with this we'll be able to get better control of patients who have a poor prognosis," said Dr Nash.

The study was sponsored by the Division of Allergy, Immunology, and Transplantation and the National Institute of Allergy and Infectious Diseases (NIAID) from the National Institutes of Health (NIH) and was conducted by the Immune Tolerance Network. Dr Nash has disclosed no relevant financial relationships. Dr Bowen reports receiving grant support from the NIH/NIAID; personal fees and research contracts from Acorda Therapeutics, Biogen IDEC, EMD Serono, Novartis, and Genzyme; and research contracts from Alexion, Avanir, Genentech, GlaxoSmithKline, Sanofi-Aventis, Osmotica, Roche, Xenoport, Opexa, and Allergan. He also consults for Teva Neuroscience and is a stockholder in Amgen. Disclosures for the other coauthors are in the paper.

Neurology. Published online February 1, 2017. Full text

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