Are you up for HSCT in MS? Do you think the ZEUS trial is a must? #MSBlog #MSResearch #CrowdSpeak
“This is another open-label descriptive study of HSCT (hematopoietic stem cell transplantation) in MS. At first glance the results are impressive and would appear better than one would expect from natural history studies. Fortunately, there were no deaths in this study. Until the community get together to plan, and perform, a proper randomised blinded study how can we, the MS community, assess the risk:benefit ratio of HSCT? HSCT is not benign and has a significant mortality associated with it. In the UK at present we really can’t refer MSers for this procedure because it is not licensed for treating MS and most HSCT units have no experience with using the procedure in MS. HSCT is close to the ultimate induction therapy and is underpinned by a very good scientific rationale. I have proposed developing the so called ZEUS trial to address the evidence gap.”
“As you can see the ZEUS trial is comparing HSCT to Alemtuzumab the only licensed induction therapy. I have suggested using a non-inferiority design simply because trying to show that HSCT is superior to Alemtuzumab will take too many MSers and be impossible to do. Before doing this study we are going to have to do a lot of enabling work to see if it feasible and whether or not MSers are prepared to take the risks associated with HSCT. I am aware that our recent survey suggests there is an appetite for the HSCT people who read and follow this blog are not average MSers and tend to be more informed. The following is a list of questions we have proposed that need answering:
- Do MSers understand the immediate risks associated with HSCT?
- Do MSers understand the undefined risks associated with HSCT?
- Would MSers be prepared to be randomised to receive alemtuzumab or HSCT?
- Would British Neurologists be prepared to refer patients for a HSCT trial?
- Do haematology units in the UK have enough capacity to handle a large national MS-HSCT trial?
- What are the economics of HSCT? How do they compare to alemtuzumab treatment?
- Would a non-myeloablative or a myeloablative protocol be best?
- What is the optimal trial protocol?
- Would we only target DMT failures or MSers naive to DMTs?
- Would eligible MSers have to have highly active MS or just active MS?
- Would the NIHR or MRC be prepared to discuss funding a trial of this nature?
- Should the study be limited to MSers with relapsing disease or should it include MSers with progressive MS?
- Should there be an age cut-off?
- Should MSer only be eligible if they have failed several other DMTs?
- Who should be the principal investigator?
- What should the primary outcome be? Relapse rate? MRI activity? Disease progression? Disability improvement?
- Should we allow retreatment if MSers breakthrough with activity as we do with alemtuzumab?
“At present we would not recommend HSCT to any of our patients. HSCT should only be done as part of clinical trials.”
Epub: Shevchenko et al. Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician’s and patient’s perspectives. Ann Hematol. 2015 Feb.
Background: High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (AHSCT) is a promising approach to treatment of MS.
Objective & Methods: In this paper, we present the long-term outcomes of a prospective single-centre study with the analysis of the safety and efficacy of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in 99 MSers: mean age-35 years old; male/female-39/60; median Expanded Disability Status Scale (EDSS) = 3.5; 43 relapsing/remitting MS, 56 progressive MS.
Results: No transplant-related deaths were observed. The mobilization and transplantation procedures were well tolerated. At 6 months post-transplant, neurological improvement or stabilization was observed in all the MSers except one. Cumulative incidence of disease progression was 16.7 % at 8 years after HDIT + AHSCT. Estimated event-free survival at median follow-up of 48.9 months was 80 %: 83.3 % in relapsing/remitting MS vs 75.5 % in progressive MS. Sixty-four MSers who did not progress during the first 3 years post-transplant and were monitored for more than 3 years were included in long-term outcome analysis. At the median long-term follow-up of 62 months, 47 % of MSers improved by at least 0.5 points on the EDSS scale as compared to baseline and exhibited improvement during the entire period of follow-up; 45 % of MSers were stable. No active, new, or enlarging lesions on magnetic resonance imaging were registered in MSers without disease progression. AHSCT was accompanied by a significant improvement in quality of life.
Conclusion: Due to the fact that MSer selection was quite different to the other studies and that the information about disease activity prior in the disease course and its treatment was inhomogeneous, comparison with the results in the literature should be done with caution. Thus, the risk/benefit ratio of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in our population of MS MSers is very favorable. The consistency of our long-term clinical and quality of life results, together with the persistence of improvement, is in favour of the efficacy and safety of this treatment approach in MS.
CoI: This group accept international referrals and charge for the procedure.
“Please note that the ZEUS Trial is one of the studies we have put forward as part of our exploration into crowdfunding. The crowdfunding survey is still open; if you haven’t done so already please feel free to complete the survey. Thank you.”