ÖGN annual conference 2023
“Flipping the pyramid” can be used to describe the new approach of turning the treatment concept for multiple sclerosis (MS) upside down and not escalating slowly, but using highly effective therapeutics right from the start. This brings stem cell transplantation back into focus, a highly effective therapy that has so far only been used in isolated cases because of its risks.
The enormous progress in the therapy of multiple sclerosis (MS) is reflected, among other things, in the fact that practitioners and patients can now choose between drugs from ten different disease-modifying substance classes. The success of the highly effective therapies has meant that the step-by-step “treat to target” concept, which starts with a moderately effective therapy (formerly also referred to as basic therapy) and escalates if necessary, has increasingly changed in recent years to the strategy to get in very effectively early on has fallen behind. Similar to other studies, a retrospective analysis of treatment data from two MS registries conducted by He et al. 2020 in Lancet Neurology It has been published that earlier initiation of highly effective therapy (within two years of disease onset) is associated with less disability at six to ten years than when these drugs are started at four to six years.
Hematopoietic stem cell transplantation
More than 20 years ago, i.e. long before many of the MS therapeutics used today came onto the market, a highly effective therapy for MS was already being discussed: Allogeneic stem cell transplantation is a therapeutic approach that potentially enables healing, but it also has to do with it because of its strong side effects carries a high risk. “In the first phase, the patients receive the peptide hormone G-CSF to mobilize the leukocytes including stem cells,” explains Priv.-Doz. dr Harald Hegen, PhD, Department of Neurology, Medical University of Innsbruck, the procedure. In the next step, these cells are removed using leukapheresis before high-dose chemotherapy (conditioning) leads to an almost complete elimination of all blood and immune cells. Finally, there is a reconstitution of the immune system from the transplant.
Superiority not clearly established
The European Group of Blood and Marrow Transplantation (EBMT) estimates the number of hematopoietic stem cell transplants performed in MS to date at approximately 1,900. In a review from 2017, the results of approval studies for MS drugs and studies on stem cell transplantation were compared with regard to the endpoint NEDA (no evidence of disease activity) after two years. At first glance, stem cell transplantation appears to be significantly more effective than drug therapy. However, the significance of the result is limited by the fact that the data was analyzed retrospectively. A randomized controlled study from 2019, in which 110 MS patients received more effective immunotherapy or stem cell transplantation after treatment failure, also showed superiority of stem cell transplantation in the parameters time to disability progression and time to the next attack. Hegen sees the main limitation of this study in the fact that not only highly effective therapies but also many basic medications were used in the comparison group. Although a recently published cohort study also suggests that hematogenous stem cell transplantation could be superior to a highly effective therapy with alemtuzumab in terms of achieving the endpoint NEDA, the current MS guidelines only attribute the potential of stem cell therapy to developing into a therapy option for relapsing MS to be able to Currently, a superiority in comparison to highly effective substances is not clearly proven. Stem cell transplantation is still considered an experimental therapy. Some current clinical studies such as BEAT-MS or RAM-MS should provide more evidence.
A central point for the cautious assessment of stem cell transplantation are safety concerns: In addition to mortality, which was 3.6% before 2005 and has now fallen to 0.3%, there are primarily long-term problems such as an increased risk of myeloproliferative diseases or a secondary autoimmunity. Patient selection is also likely to be important: Younger patients who are able to walk and have a short disease duration and a relapsing and highly active course of the disease are currently considered possible candidates for a stem cell transplant.
Annual Meeting of the Austrian Society of Neurology, Bregenz, March 24, 2023