ECTRIMS 2025: Stem cell transplant beats DMTs at lowering risk of PIRA
Data show aHSCT reduces long-term PIRA better than Tysabri, other DMTs
A stem cell transplant may offer better long-term results for people with aggressive multiple sclerosis (MS) compared with standard high-efficacy drug treatment, according to new evidence presented at a major European conference this week.
Specifically, researchers found that an autologous hematopoietic stem cell transplant (aHSCT) was superior to treatment with Tysabri (natalizumab) followed by other disease-modifying therapies (DMTs) at preventing long-term disability worsening, especially the “silent progression” known as PIRA (progression independent of relapse activity).
Alice Mariottini, MD, PhD, of the University of Florence and the Careggi University Hospital in Italy, presented the data, comparing the two treatment strategies in people with aggressive relapsing-remitting MS (RRMS).
Mariottini shared the data at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis, held Sept. 24-26 in Barcelona, Spain, and online, in a presentation titled “Autologous haematopoietic stem cell transplantation halts long-term PIRA in aggressive relapsing-remitting MS: a matched comparative study.”
Understanding MS and PIRA
MS is an autoimmune condition in which the immune system mistakenly launches inflammatory attacks against healthy parts of the central nervous system (CNS), including the brain and spinal cord.
The majority of patients are first diagnosed with RRMS, where relapses, or periods of sudden symptom worsening, are interspersed with periods of remission during which symptoms ease.
Disability can accumulate in these patients if they fail to recover adequately from a relapse, but it’s now recognized that disability progression can also occur in the absence of acute disease flares. This silent progression is called PIRA.
Most currently available DMTs do not readily enter the CNS, according to Mariottini. Instead, they work largely in the rest of the body, or periphery, to control immune activation and inflammation.
This means they may have a limited effect on PIRA, which is thought to be mainly driven by chronic inflammation in the CNS.
aHSCT, commonly known as a stem cell transplant, aims to reset the faulty immune system in MS. The procedure involves collecting a person’s hematopoietic stem cells — the precursors to most immune cells — then treating them with chemotherapy to eliminate existing dysfunctional immune cells in the body. The stem cells are then infused back into the patient to repopulate the body with healthy immune cells.
This approach is used in severe cases of RRMS that have not responded to high-efficacy DMTs. Notably, the chemotherapy agents used for aHSCT can also cross into the CNS, offering an advantage for targeting the CNS inflammation thought to drive PIRA.
With that in mind, Mariottini and colleagues evaluated the effect of aHSCT on long-term PIRA in aggressive RRMS. They retrospectively analyzed data from patients seen at a hospital in Italy from 2007 to 2018, comparing clinical outcomes between 30 people who received aHSCT and 30 who were treated according to clinical practice with Tysabri followed by other DMTs.
Of the patients in the DMT group, 29 who started on Tysabri ultimately switched. Most often (79%), this was due to testing positive for the John Cunningham virus, which can cause a severe brain infection called progressive multifocal leukoencephalopathy in people with compromised immune systems.
The data showed the proportion of patients with PIRA was “remarkably lower” in the aHSCT group, remaining at 10% from years five to 10 of follow-up. In the DMT group, the PIRA rate was 21% after five years and 49% after 10 years.
Better long-term outcomes
aHSCT was also superior in other clinical outcomes, leading to significantly lower rates of disability worsening than DMTs (10% vs. 65%). One relapse occurred in the aHSCT group and it did not result in long-term disability worsening. In the DMT group, 81% of patients relapsed.
Moreover, 90% of people who underwent aHSCT had NEDA-3 after five years — meaning they experienced no relapses, MRI activity, or confirmed disability worsening during this period — and 76% retained that status at year 10 after transplant. By comparison, 16% of the DMT group met NEDA-3 criteria after five years, and none did after 10 years.
The proportion of patients converting to secondary progressive MS also was significantly lower with aHSCT than with DMTs — 7% vs. 21% at year five and 7% vs. 32% at year 10.
No patients who underwent aHSCT died over the course of follow-up, while two people in the DMT group died due to complications of advanced disease.
“In conclusion, our study shows that aHSCT reduced the long-term risk of PIRA compared to DMTs and provided higher rates of suppression of new focal inflammatory activity,” Mariottini said.
Timely treatment with aHSCT — or other DMTs capable of targeting inflammation in both the CNS and periphery — could “radically change disability trajectories over time,” she noted.
Mariottini concluded that there is now a need to find biomarkers capable of identifying cases of aggressive MS in which early use of aHSCT, before other treatments fail, may be beneficial.
Note: The Multiple Sclerosis News Today team is providing live coverage of the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Sept. 24-26. Go here to see the latest stories from the conference.
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