Autologous hematopoietic stem cell transplantation (aHSCT) has been used in the treatment of multiple sclerosis (MS) since 1995 and was approved in Switzerland in June 2018. In their presentation ‘Stem cell transplantation in MS: What have we learnt from practice’ at the MS State of the Art Symposium, Dr Ilijas Jelcic and Prof. Dr Roland Martin presented the safety and efficacy data from the first patients in Switzerland to undergo this treatment at the University Hospital Zürich (UZH).¹

The case for aHSCT

After 2 years of high efficacy disease modifying therapies (DMTs), 13–46% of treated patients show NEDA-3 (no evidence of disease activity). Patients who undergo stem cell transplantation show considerably improved NEDA-3 of 78–83% and 60–68% at 2 and 5 years, respectively.²

Who were the patients?

For a patient to be considered for aHSCT in MS, they had to meet certain criteria as defined by the Federal Office of Public Health (FOPH). These included: 1) Breakthrough activity of MS despite being on highly effective DMTs, 2) Indication as set by the interdisciplinary haemato-neuroimmunological board at the UZH, and 3) Participation in the aHSCT-in-MS registry for 5 years. It was the patient data from this registry that was presented in the symposium. At baseline, median age was 40 years, median disease duration 9.1 years and median EDSS (Expanded disability status scale) of 4.0. Nearly half of the patients (45.7%) had relapsing-remitting MS (RRMS), while the remaining had progressive MS (PMS).

What were the main findings from the study?

Dr Jelcic presented the main findings from the study with regards to the patients. The centre at the UZH followed the BEAM-ATG protocol in all patients. Median post-aHSCT follow-up was 23 months. EDSS improvement, stabilisation and worsening were observed in 20 (57%), 8 (23%) and 7 (20%) out of 35 patients, respectively. Among the patients who showed EDSS improvement, a majority (68.8%) had RRMS, while most patients who showed EDSS worsening had PMS (71.4%). Additionally, there were two instances of death by assisted suicide reported in the PMS group, despite EDSS-stable follow up and NEDA-3 status. This highlighted the need for additional psychiatric evaluations and support for patients considering aHSCT. Prof. Martin discussed the potential mechanisms for immune renewal with this therapy, in the context of MS. Given the importance of B-cells and T-lymphocytes in MS, and their influence on disease progression, these cells were the focus of their study. The T-cell receptor (TCR) repertoire of CD4+ effector memory cells showed an approximately 25% overlap early after HSCT but decreased over time. The TCR repertoire of CD4+ naïve T-cells was completely renewed after 12 months. B-cells were found to reconstitute fast and in the order of their sequential maturation stages.

What are the key takeaways?

aHSCT-in-MS using the BEAM-ATG protocol induced a high rate of disease stabilisation, and even showed improvements in patients who had previously experienced prior breakthrough disease activity including those patients on high efficacy DMTs. The effect appears to be more pronounced in cases of RRMS, however further investigations and a longer follow up are needed. The presenters believe that the overall safety was acceptable, but additional monitoring is required, including for infectious diseases, as well as psychiatric evaluations after transplantation.

Currently a-HSCT-in-MS is approved only at the UZH. There are ongoing discussions with the FOPH to have at least one centre in each language zone. The success of the programme requires excellent collaborations between the MS centre, and the transplant experts/haematologists.

Read more MS State of the Art Symposium 2022 coverage by following this link.

References

1. Sormani et al. Multiple Sclerosis Journal. 2017;23(2):201–204.
2. Dr Ilijas Jelcic and Prof. Dr Roland Martin, ‘Stem cell transplantation in MS: What have we learnt from practice’ Presented at MS state of the Art Symposium, January 31, 2022.