New Evidence Sheds Light on Stem Cell Transplantation for Progressive MS

Autologous hematopoietic stem cell transplantation (AHSCT) was not superior in preventing relapses or reducing disability progression than natalizumab (Tysabri) in progressive multiple sclerosis (MS), new research suggested.

Patients with progressive MS, advanced disability, and low pre-treatment relapse activity who had AHSCT experienced similar on-treatment frequency of relapses as matched patients treated with natalizumab over up to 6 years, according to Tomas Kalincik, PhD, of the Royal Melbourne Hospital in Australia.

Cumulative hazards of confirmed worsening on the Expanded Disability Status Scale (EDSS) and disability improvement also were similar, Kalincik said in a late-breaking presentation at the 2022 meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“What we know about the use of AHSCT in progressive disease is mostly fueled by information we have learned primarily through relapse and remitting disease,” Kalincik said. Chemotherapy followed by AHSCT is used to treat aggressive forms of relapsing MS and “occasionally people with progressive disease forms may be exposed to this therapy,” he pointed out.

A recent Italian cohort study showed AHSCT was associated with slower progression of disability compared with a matched composite group of disease-modifying therapies. “But patients with progressive MS tended to accumulate disability more often than those with relapsing MS,” Kalincik noted. “And unlike in relapsing MS, where you see the stabilization of disability, we did not see the same trend in progressive disease.”

Kalincik and colleagues studied people with secondary or primary progressive MS from six AHSCT MS centers around the world and participants in the international MSBase registry.

People were included in the study if they received AHSCT or started natalizumab during progressive MS. Natalizumab was chosen as a comparator because ocrelizumab (Ocrevus) had not been approved in several locations during the course of the study, Kalincik said.

Participants were propensity score-matched on sex, age, EDSS score, number of relapses 12 and 24 months before baseline, time from MS onset, most effective prior therapy, and country (EDSS scores range from 0 to 10, with higher numbers representing more disability). Participants were followed for up to 6 years.

Overall, 39 people who received AHSCT and 65 natalizumab-treated patients were matched. Mean EDSS at baseline was 5.7 in both groups, indicating moderately advanced disease. The AHSCT group had a mean baseline age of 36.8 and 35.9% were men. The natalizumab group had a mean baseline age of 43.9 and 30.8% were men. In both groups, most patients had secondary progressive disease.

The mean annualized relapse rate (ARR) was 0.08 with AHSCT and 0.08 with natalizumab. The hazard ratio (HR) for relapses was 1.05 (95% CI 0.39-2.82, P=0.92).

Cumulative hazards of 6-month confirmed worsening on EDSS (HR 1.49, 95% CI 0.70-3.14. P=0.30) and confirmed disability improvement (HR 1.50, 95% CI 0.22-10.28, P=0.67) also were similar. “Confirmed disability improvement was rarely observed both in the AHSCT and natalizumab groups,” Kalincik said.

At year 2, the probability of disability worsening was 36% with AHSCT and 22% with natalizumab. At year 5, those probabilities were 45% with AHSCT and 22% with natalizumab.

In the AHSCT group, three patients (7.7%) experienced febrile neutropenia, nine (23%) had serum sickness, six (15%) required ICU admission, and 36 (92%) developed complications after discharge, including 21 infections. No treatment-related deaths were reported.

The analysis had several limitations, Kalincik acknowledged. There was no randomization and cohort sizes were small. The cohorts could not be matched on MRI, and MRI data were not available as an outcome. In addition, complete safety data were not available for the natalizumab group.