Stem Cell Transplant Benefits in Secondary Progressive MS

October 21, 2021

Autologous hematopoietic stem cell transplantation for the treatment of active secondary progressive MS is associated with better disability outcomes than other immunotherapies, a new Italian study suggests.

In the study, stem cell transplant was associated with a slowing of disability progression and a higher likelihood of disability improvement in patients with secondary progressive multiple sclerosis compared with other disease-modifying therapies.

"Our study shows that, although limited, sustained disability improvement is still possible during early active secondary progressive MS and seems to be more likely with stem cell transplant than other disease-modifying treatments," said lead author Giacomo Boffa, MD, University of Genoa, Italy.

"Brain penetrating-intent immune suppression in long-term immunological reconstitution within the central nervous system could be responsible for this clinical efficacy," he added.

Boffa presented the research at the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2021, held October 13-15.

He explained that compartmentalized inflation in the brain parenchyma, left meninges, and the cerebral spinal fluid (CSF) is a key driver of disability worsening in secondary progressive MS.

Although initial studies did not reveal an effect of disease-modifying therapies in secondary progressive MS, recent randomized trials have established some benefit of siponimod in reducing the risk of disability worsening and, consistent with this finding, observational studies have suggested other available immunotherapies may also be beneficial for active secondary progressive MS, Boffa noted.

"Autologous hematopoietic stem cell transplantation has been widely investigated for the treatment of refractory MS, and although the ideal candidate for this procedure is a young patient with relapsing-remitting MS, there is some evidence to suggest that the procedure could also slow down neurological disability in patients with secondary progressive MS," Boffa said.

"Indeed, all the drugs used in the transplant technology share the ability to cross the blood–brain barrier and exert a strong immunosuppressant effect within the brain parenchyma and CSF," he added.  

The aim of the current study was to compare the effect of autologous hematopoietic stem cell transplantation with other immunotherapies on disability worsening in patients with active secondary progressive MS.

Study endpoints included the Expanded Disability Status Scale (EDSS) score, 6-month worsening and improvement in disability, and sustained disability improvement over time.

The researchers studied patients with secondary progressive MS who had received autologous hematopoietic stem cell transplantation and were included in the Italian Bone Marrow Transplant Group. They were compared with a control group of patients in the Italian MS registry who had started a nontransplant disease-modifying therapy after the diagnosis of secondary progressive MS.

To control for many different variables, two separate analyses were preformed. One analyses was a propensity-score approach (patients were matched based on their propensity to receive bone marrow transplant or one of the other disease-modifying therapies). The other analysis used an overlap weighting approach (each patient was given a weight proportional to the probability of them belonging to the other treatment group).

The final cohort consisted of 79 bone marrow transplant recipients and 1975 patients who had received other disease-modifying therapies.

Before matching, patients in the control group were older, had a longer disease duration, and had a lower annualized relapse rate than transplanted patients.

After propensity-score matching, there were 69 transplanted patients and 217 control patients who were well balanced in terms of clinical and demographic characteristics. After overlap weighting, the entire cohort was also well balanced for these variables.

In terms of the primary endpoint, stem cell transplant stabilized the EDSS score over time, while patients treated with other disease-modifying therapies had continuous progression of the EDSS score over time.

In the propensity-matched analysis, the EDSS score improved by 0.013 points per year in the stem cell transplant group compared with a worsening of 0.157 points per year in the control group. Similar results were seen in the overlap-weighting analysis.  

The effect of stem cell transplant on EDSS score translated into a significantly delayed time to confirmed disability progression in the stem cell transplant group compared with the control group (HR, 0.5; P = .005), Boffa reported.

Five years after the procedure, 62% of the transplant group were free of disability progression, compared with around 20% of the control group.  

Patients in the transplanted group were also more likely to show disability improvement over time. Five years after the procedure, almost 20% of the stem cell transplant group still maintained a disability improvement compared with only 4% of patients treated with other disease-modifying therapies.

"Our study population was composed of relatively young patients (average age 38 years) with clinical activity during secondary progressive MS, and the results of this study would not be applicable to patients with secondary progressive MS patients without signs of inflammatory activity," Boffa commented.

"But on the other hand, our results reinforce the notion that ongoing inflammation during progressive MS requires adequate immunotherapy," he added.   

ECTRIMS Congress. Presented October 14, 2021.

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