Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study

Abstract

Background: A growing evidence base supports the use of autologous haematopoietic stem cell transplantation (aHSCT) for treatment of relapsing-remitting multiple sclerosis (RRMS), but it has not yet been integrated into most national clinical guidelines. The objective of this study was to assess efficacy and safety when aHSCT is implemented in routine healthcare.

Methods: We assessed 231 patients and the final analysis included 174 RRMS patients who were treated with aHSCT in Sweden before 1 January 2020. Efficacy was evaluated by performing a retrospective analysis of prospectively collected data from the Swedish MS registry. Procedure-related safety was assessed by analysing data from electronic patient records covering a period of 100 days following aHSCT.

Results: With a median follow-up time of 5.5 (IQR: 3.4-7.5) years, the Kaplan-Meier estimate for no evidence of disease activity was 73% (95% CI 66% to 81%) at 5 years and 65% (95% CI 57% to 75%) at 10 years. Out of the 149 patients with baseline disability, 80 (54%) improved, 55 (37%) were stable and 14 (9%) deteriorated. The mean number of adverse events per patient was 1.7 (±SD: 1.5) for grade 3 events and 0.06 (±SD: 0.3) for grade 4 events. Febrile neutropenia was the most common adverse event, affecting 68% of patients. There was no treatment-related mortality.

Conclusions: Treatment with aHSCT for RRMS is associated with freedom from disease activity in a majority of patients, with acceptable adverse events. This procedure should be considered a standard of care for patients with highly active RRMS.

Keywords: CLINICAL NEUROLOGY; HAEMATOLOGY; MULTIPLE SCLEROSIS.

Figure 1

In this study, a total of 231 patients were evaluated for potential inclusion, with 174 ultimately being incorporated into the final analysis. Fifteen patients were excluded as they failed to meet the inclusion criteria, which required a diagnosis of multiple sclerosis (MS), a relapsing-remitting disease course and autologous haematopoietic stem cell transplantation (aHSCT) performed for MS at any of the seven Swedish transplantation centres before 1 January, 2020. Thirty patients had progressive MS at aHSCT and were excluded. An additional 12 did not fulfil the requirements for the minimal dataset, which were data on disease course at the time of transplantation, date of transplantation, data on conditioning regimen and at least one follow-up visit. EBMT, European Society for Blood and Marrow Transplantation; SMSreg, Swedish MS registry.

Figure 2

Current and previous treatments. This Sankey diagram shows disease-modifying treatments used before and after autologous haematopoietic stem cell transplantation (aHSCT). Twenty-three patients had not used any disease-modifying treatment prior to aHSCT. ALZ, alemtuzumab; DMF, dimethyl fumarate; FLM, fingolimod; GLA, glatiramer acetate; IFN, interferon; IVIG, intravenous IgG; MTX, mitoxantrone; NZB, natalizumab; RTX, rituximab; TMF, teriflunomide.

Figure 3

Primary and secondary endpoints. Kaplan-Meier curves for the primary endpoint: no evidence of disease activity (NEDA), and for the secondary endpoints: freedom from MRI events, freedom from clinical relapses and freedom from confirmed disability worsening (CDW).

Figure 4

Changes in disability over time. Proportions of patients with confirmed disability improvement (CDI), stable disability and confirmed disability worsening (CDW) at different timepoints. Scores on the Kurtzke Expanded Disability Status Scale (EDSS) at baseline were compared with the EDSS scores at 3, 5 and 10 years as well as with the EDSS scores at last follow-up. Only patients with some degree of disability (EDSS≥2) were taken into account for this analysis.

Figure 5

Proportions of patients with different levels of disability over time. Disability strata defined using the Kurtzke Expanded Disability Status Scale (EDSS) from baseline and over the first 3 years after autologous haematopoietic stem cell transplantation. No disability was defined as EDSS 0–1.5, mild-to-moderate disability as EDSS 2–3.5, significant disability as EDSS 4–5.5, severe disability as EDSS 6–6.5 and very severe disability as EDSS 7–9.5.