Positive Stem Cell Transplant Data Are Increasing Its Use

COPENHAGEN — As a rescue intervention for multiple sclerosis (MS), hematopoietic stem cell transplant (HSCT) is being offered with greater frequency at centers experienced with this approach.

With only one completed randomized trial available, HSCT remains experimental, but the number of patients treated with this approach has now reached substantial numbers over 20 years of experience at multiple centers, according to two representative real-world studies presented at the 2024 ECTRIMS annual meeting.

The latest data are wholly consistent with a 2019 multinational randomized trial that found HSCT, which is a one-time intervention, to be relatively well tolerated and more effective than disease-modifying therapy (DMT) for median time to progression in patients refractory to DMT.

Relative to 24 months in the DMT group, median time to relapse was not reached among those randomized to HSCT because there were too few events. The hazard ratio (HR) reduction for progression was greater than 90% (HR, 0.07; P < .001). Other endpoints, such as EDSS, which improved in the group receiving HSCT but declined on DMT, also favored the single-treatment therapy.

Two Real-World Experiences With HSCT Reported

Of the two multicenter real-world studies presented at ECTRIMS, one included 363 patients treated at 1 of 14 participating public hospitals in the United Kingdom since 2002. This analysis was uncontrolled. The other, with 97 patients treated at one of 20 participating centers in Italy since 1999, compared HSCT to alemtuzumab retrospectively.

In the UK data, presented by Paolo Muraro, MD, PhD, senior consultant, Division of Brain Sciences, Imperial College London, England, 94.6% were in relapse-free survival (RFS) at 2 years and 88.6% at 5 years after undergoing HSCT. He called these numbers “impressive.”

In addition, MRI-free activity survival (MFS) was 88.2% and 78.8% at 2 and 5 years, respectively, Dr Muraro said.

On the Expanded Disability Status Scale (EDSS), the cumulative incidence of improvement was 24.6% at 2 years and 28.6% at 5 years. There was no evidence of disease activity on the endpoints of symptoms, relapse, and MRI (NEDA-3) in 72% of patients at 2 years and 48.5% at 5 years.

Relative to historical response rates in a refractory population, Dr Muraro considered these results favorable. Although there were four deaths, producing a treatment-related mortality of 1.1%, all occurred at an early stage of the HSCT program when there was limited experience in the management of cytopenias and other acute complications of HSCT.

“In this real-world cohort, stem cell transplant led to a durable remission of inflammatory activity and to clinical stability even though this included patients with a high EDSS at baseline [median, 6.0] and a substantial proportion [39%] with progressive disease,” Dr Muraro said.

In the Italian data, presented by Alessio Signori, MD, PhD, associate professor, Department of Health Sciences, University of Genoa, Italy, the 97 HSCT patients were matched with 314 treated with alemtuzumab over the same period and compared with propensity score overlap weighting. Baseline features were comparable.

HSCT Outperforms Alemtuzumab on All Measures

After a median follow-up of 62 months in the HSCT group and 30 months in the alemtuzumab group, HSCT outperformed drug therapy on all efficacy measures. When translated into HR, HSCT relative to alemtuzumab was associated with a 50% reduction in the probability of disability progression (HR, 0.50; P = .025), a 66% reduction in probability of relapse (HR, 0.34; P < .001), and a 62% reduction in the probability of MRI activity (HR, 0.38; P < .001).

“At 5 years, 58.3% of patients in the HSCT group versus 22.3% of the patients in the alemtuzumab group maintained NEDA-3,” said Dr Signori, who reported that this difference represented a greater than 50% reduction (HR, 0.48; P < .001).

In this study, there were two treatment-related deaths. Both occurred within 30 days of HSCT and, again, were confined to the early experience with HSCT.

There are questions that remain unanswered, such as whether there are predictors of response to HSCT. Although sustained responses have been greater on HSCT than drug therapy on average, poor responses appeared to be more common among those with a progressive phenotype in the UK experience.

Although patients with progressive disease were excluded from the Italian study, a real-world experience published 2 years ago also indicated that patients with progressive forms of MS respond less well to HSCT. Conducted in the United States at a single center (Northwestern University, Chicago) with 414 patients of whom 93 had progressive disease, EDSS progressively declined over the 5 years of follow-up among those with secondary progressive MS even as it improved in those with relapsing-remitting multiple sclerosis.

HSCT Considered on Compassionate Basis

Overall, the HSCT experience as a rescue therapy for MS patients with an inadequate response to DMT has led a growing number of centers active in this area to offer this option on a compassionate basis, according to Dr Muraro and Dr Signori. Joachim Burman, MD, PhD, who was the moderator of the scientific session at ECTRIMS and the leader of a research program into HSCT for MS at Uppsala University, Uppsala, Sweden, agreed.

The increasing number of centers offering HSCT to MS patients does not preclude the need or the value of the ongoing phase 3 trials, according to Dr Burman, but he suggested that there is a growing focus of how it should be used, not whether it will be used.

Ultimately, he speculated that HSCT, once accepted as a mainstream option for MS, will probably be confined to the 5%-10% of patients with very aggressive disease. This is not for lack of safety or efficacy, but he sees several barriers to using this approach first-line, outside of special situations.

“You need a team of several different specialists to offer HSCT,” he said, suggesting that this approach to MS is much more complicated than a visit to a neurologist’s office for a DMT prescription. However, he thinks other barriers, such as concern about safety, are dissipating.

HSCT “is still being characterized as a high-risk procedure, but I would object to that,” he said. “The deaths associated with HSCT largely occurred 20 years ago when the field was new.”

Dr Muraro reported a financial relationship with Cellerys AG that is unrelated to this study. Dr Signori reported financial relationships with Chiesi, Horizon, and Novartis. Dr Burman reported no potential conflicts of interest.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.