#ECTRIMS2022 – Analyses Weigh Stem Cell Transplant Versus DMTs

Autologous hematopoietic stem cell transplant (aHSCT) is superior to Gilenya (fingolimod) and Tysabri (natalizumab) at preventing relapses and reducing disability in people with highly active relapsing-remitting multiple sclerosis (RRMS).

In turn, aHSCT appears to be as effective as Ocrevus (ocrelizumab) in RRMS patients and also was not superior to Tysabri in people with progressive MS.

These are the findings of retrospective and comparative analyses of patients with similar demographic and clinical parameters before receiving either aHSCT or approved disease-modifying therapies (DMTs).

The results were shared in two oral presentations at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held Oct. 26–28 both virtually and in Amsterdam, the Netherlands.

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Both were presented by Tomas Kalincik, MD, PhD, Dame Kate Campbell professorial fellow at the University of Melbourne, in Australia, and the head of the Royal Melbourne Hospital’s MS Center.

aHSCT is an intensive, experimental treatment approach meant to stop MS’  abnormal immune attacks and inflammation on the brain and spinal cord by resetting a patient’s immune system.

The procedure begins with the collection of a person’s own healthy blood cell progenitors, also known as hematopoietic stem cells, from the blood or the bone marrow. These cells are then infused back to the patient after a fairly aggressive chemotherapy regimen is given to kill their immune cells.

While this one-time treatment has the potential to slow or halt MS progression, its experimental status has limited its use to patients with aggressive forms of the disease, mostly with relapsing MS, and who have failed to respond to approved therapies.

Some previous studies suggested this approach is effective — and more so than some DMTs — at preventing relapses and disability progression in people with relapsing forms of MS. But evidence on its effects on progressive MS is much more limited.

Comparing aHSCT to DMTs

Now, an international team of researchers compared aHSCT’s efficacy against high-efficacy DMTs in RRMS patients and in people with secondary progressive (SPMS) or primary progressive MS (PPMS).

The analyses included patients given the stem cell transplant at six aHSCT MS centers in Canada, the U.K., Sweden, Norway, and Australia. As controls, researchers examined patients receiving a DMT who were on MSBase, an international real-world registry of people with MS and other neuro-immunological diseases.

Eligible patients were those receiving, for the first time, aHSCT or either one of three high-efficacy DMTs (Gilenya, Tysabri, or Ocrevus) in the case of RRMS patients, or Tysabri in progressive MS patients, and who had enough data available before and after treatment.

Mathematical modeling was used to ensure that aHSCT-treated patients had similar pre-treatment demographic and clinical features to those given each of the DMTs. These features included age, sex, disability status, time from disease onset, number of relapses, prior DMTs, and geographic location.

The researchers then compared two groups for annualized relapse rates (ARRs), risk of first relapse, and six-month confirmed disability worsening and improvement, based on sustained changes in the expanded disability status scale (EDSS) score.

More findings

Findings from RRMS patients were shared in the presentation, “Comparative effectiveness of autologous hematopoietic stem cell transplantation vs. fingolimod, ocrelizumab and natalizumab in relapsing-remitting MS.”

For the analyses, the outcomes of 144 patients given the stem cell transplant were compared with those of 769 matched patients on Gilenya. Also, 146 aHSCT-treated patients were matched with 730 patients treated with Tysabri, and 110 patients on the aHSCT group were matched with 343 patients given Ocrevus.

The matched populations had very high relapse activity before treatment (about 0.8 relapses per year in the prior year) and moderate disability.

Results showed that, compared with Gilenya, aHSCT was associated with a significantly lower ARR (mean of 0.09 vs. 0.19 relapses per year), a 74% lower risk of first relapse, and a 2.7 times higher chance of disability improvement (meaning less disability). No significant differences were observed in terms of risk of disability worsening.

When comparing aHSCT to Tysabri, the team found “a statistically significant but clinically marginal difference” in ARR (0.08 vs. 0.10 relapses per year), Kalincik said. Patients on aHSCT also had a 49% lower risk of experiencing a first relapse, though Kalincik also noted this was “a relatively marginal difference.”

Still, the stem cell transplant was linked to a nearly 2.7 times higher chance of disability improvement — mainly in the first year of follow-up — but similar probability of disability worsening.

Finally, aHSCT was comparable to Ocrevus in ARR, risk of relapse, and probability of both disability worsening and reduction, but the shorter follow-up duration in these groups (up to three years) may have “limited the power of this particular comparison,” Kalincik said.

These findings highlight that, among RRMS patients with highly active disease and moderate disability, “aHSCT is substantially superior to [Gilenya] and marginally superior to [Tysabri] in reducing the risk of post-treatment relapses,” Kalincik said.

“We have found no evidence of a difference in disability [worsening] outcomes over three to five years of available follow-up, but we found a superior possibility of disability improvement facilitated by aHSCT when compared to [Gilenya or Tysabri],” Kalincik added.

Analysis involving Tysabri

Results from people with progressive forms of MS were detailed in the second presentation titled, “Effectiveness of autologous hematopoietic stem cell transplantation in comparison with natalizumab in progressive MS.”

The analysis included 39 patients treated with aHSCT (37 with SPMS and two with PPMS) and 65 matched Tysabri-treated patients (53 with SPMS and 12 with PPMS). These patients had moderately advanced disability and moderate pre-treatment relapse activity, with a mean of 0.5–0.6 relapses per year in the previous 12 months. 

Up to five years of data showed that aHSCT and Tysabri resulted in similarly low relapse rates (mean of 0.08 relapses per year for both groups), as well as comparable risk of first relapse. The two treatments also led to similar rates of confirmed disability worsening and improvement — the latter being “very rarely observed,” Kalincik said.

Despite the limited number of included patients, the results indicate that “aHSCT is not superior to [Tysabri] in reducing disability progression, in facilitating disability improvement, or reducing subsequent relapses,” Kalincik said.

Regarding aHSCT’s safety, the most commonly reported adverse events were complications after discharge, most often infections (36% in RRMS, and 92% in progressive MS).

Other common adverse events included febrile neutropenia (fever with low counts of a type of white blood cell), hypersensitivity reaction, and intensive care unit admission. One treatment-related death was reported among the 159 RRMS patients treated with aHSCT (0.6%) and in none of the 39 progressive MS patients.

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ECTRIMS Forum 2022 Oct. 26–28. Go here to see the latest stories from the conference.