Stem Cell Transplant Effective as First Line in Aggressive MS

October 15, 2018

BERLIN — More very encouraging data on the use of autologous stem cell transplant in multiple sclerosis (MS) have been presented. There was no evidence of disease activity post transplant in patients who previously had extremely aggressive disease.

The case series of 20 patients was reported at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018 here by Joyutpal Das, MBBS, Royal Hallamshire Hospital Sheffield, United Kingdom.

"What is particularly new and interesting about these patients is that they did not have any other disease-modifying treatments before stem cell transplant," Das commented to Medscape Medical News. "We used this as a first-line treatment in patients presenting with a very aggressive form of MS. These patients were becoming disabled very quickly, so they needed something extremely effective to impact their disease.

"We have median follow-up of 2.5 years, and there were no post-transplant clinical relapses, no MRI activity following the 6-month MRI scan, an improvement in disability scores in 95% of patients, and no patient has had disability progression post transplant," he concluded.

As far as he is aware, this is the largest case series of treatment-naive patients who underwent stem cell transplant, he noted. "Normally, this treatment would be given when patients fail on standard disease-modifying therapy. Our results suggest that stem cell treatment for MS is now becoming a safe and highly effective for patients with very active disease," Das added.

Commenting for Medscape Medical News, Mark Freedman, MD, Ottawa Hospital, Ontario, Canada, who is also involved in the field of stem cell transplantation for MS, called the data, "extremely encouraging."

"This a different cohort that has been generally studied in stem cell transplant treatment in MS," he said. "They are treatment-naive and have extremely aggressive disease — they are like runaway trains. But the disease is stopped after stem cell transplant."

Chair of the session at which the case series was presented, Howard L. Weiner, MD, Harvard Medical School, Boston, said, "There is absolutely no doubt that stem cell therapy is very effective — these results reinforce that.

"The big question is, what happens over time — in 10 or 15 years," he added. "Do these patients become progressive or not? They only have 2-year follow- up in this study — that's not nearly enough. We need 10-year follow-up at least."

But Freedman said his group now has follow-up for up to 20 years for some of their first patients who received stem cell transplants, and these patients are continuing to show an impressive lack of disease activity.

"Some patients were progressive to start with, but of those who had relapsing remitting MS, none have yet developed progressive disease," he said.

Freedman said the case series presented at ECTRIMS "is totally in line" with his group's results. "We saw absolutely no evidence of disease activity after the transplant — substantial recoveries — they don't need anything else."

The current case series presented by Das comprised 20 patients from five centers in five countries, the United States, Canada, the United Kingdom, Sweden, and Italy.

The patients' mean age at diagnosis was 28 years (range, 17 - 47 years). All were given stem cell transplants within the same year. The mean interval between diagnosis and treatment was 5 months. Before transplant, they experienced frequent relapses, incomplete recovery after relapses, and had multiple gadolinium-enhancing lesions. In addition, for many patients, there was involvement of brainstem, cerebellum, and spine.

One patient displayed MRI activity at the 6-month timepoint; thereafter, no patients showed any MRI activity.

Expanded Disability Status Scale (EDSS) scores improved for 95% of patients. Before treatment, the median EDSS score was 6.5 (range, 1.5 - 9.5); at last follow-up, the median EDSS score was 2.0 (range, 0 - 6.5).

Das noted that safety of stem cell transplant has much improved in recent years.

"Mortality rates associated with stem cell transplant have significantly improved over the years. Historically, there was a mortality rate of 3% to 4%, but recent data from the European Group for Blood and Marrow Transplantation Society report only one death between 2012 and 2016," he said.

He suggested there were two main reasons for this. "We are choosing patients more carefully, and we are using lighter conditioning regimens.

"I would absolutely say that stem cell treatment is now a real option for a small population of patients — when the disease is very active and the patient is young," he said.

Freedman said about 60 MS patients have received stem cell transplants at his hospital. "Our original cohort of 24 patients received transplants starting in the year 2000. The latest results in these patients were published in the Lancet in 2016. We've now treated an additional 30 or 40 patients. They are all doing well."

Six patients in original group continued to get worse early on after transplant, he added, "but we think that was due to previous disease before the transplant. There can be an early degenerative phase, but that levels off quite quickly."

But Freedman cautioned that this treatment is certainly not appropriate for most MS patients.

"This is a big undertaking," he said. "The procedure itself can be very grueling. Younger patients can endure it better, but it leaves them sterile, which could be an issue. However, three of our patient have gone on to have babies with frozen or donated eggs. But yes, this procedure should be reserved for patients with very aggressive disease."

He added: "It is very hard to strictly define who should have this therapy. What we've said in the past is evidence of early, aggressive, active, destructive disease. These patients are normally also young."

Safety is "also obviously a caveat," he added. "Just like you wouldn't have your appendix out at the corner store, these patients we are reporting have been treating at centers which have done hundreds or thousands of stem cell transplants. Dedicated teams of people are managing post-transplant care, which is almost as important as the transplant itself.

"Because we can do transplants with pretty good morbidity stats at our center, we would offer it as an alternative to some of our younger patients with the most aggressive disease," he concluded. "I would say a little less than 10% of MS patients could possibly qualify for such therapy. But fortunately, most patients respond to drug therapy, so we don't have to pull out all stops like that."

The authors have disclosed no relevant financial relationships.

34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018. Abstract 230, presented October 11, 2018.

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