New evidence sheds light on stem cell transplantation in progressive MS

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

According to Tomas Kalincik, PhD, of Royal Melbourne Hospital, patients with pre-treatment MS, advanced disability, and low relapse activity who had undergone AHSCT had a similar on-treatment rate of recurrence as matched patients who had undergone up to 6 months of treatment years were treated with natalizumab in Australia.

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

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

A recent Italian cohort study showed that AHSCT was associated with slower disability progression compared to a matched composite group of disease-modifying therapies. “But patients with progressive MS were more likely to accumulate disability than those with relapsing MS,” Kalincik noted. “And unlike in relapsing remitting MS, where you see the disability stabilizing, we haven’t seen the same trend as the disease progressed.”

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 an AHSCT or started natalizumab during progressive MS. Natalizumab was selected as the comparator because ocrelizumab (Ocrevus) had not been approved at several sites during the course of the study, Kalincik said.

Participants were analyzed for gender, age, EDSS score, number of relapses 12 and 24 months prior to study entry, time since onset of MS, most effective prior therapy, and country (EDSS scores range from 0 to 10, with higher numbers indicating more disability). . Participants were followed for up to 6 years.

A total of 39 subjects who received AHSCT and 65 subjects treated with natalizumab were matched. The mean EDSS score at baseline was 5.7 in both groups, indicating moderately advanced disease. The AHSCT group had a mean baseline age of 36.8 years and 35.9% were males. The natalizumab group had a mean baseline age of 43.9 and 30.8% were males. In both groups, most patients had secondary progressive disease.

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

Cumulative hazards of worsening confirmed at 6 months with 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) were also similar. “Confirmed improvement in disability was rarely seen in both 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, these 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 post-discharge complications, 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 a result. In addition, full safety data were not available for the natalizumab group.