Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing–remitting multiple sclerosis: an observational study

Abstract

ObjectiveTo compare outcomes after treatment with autologous haematopoietic stem cell transplantation (AHSCT) and alemtuzumab (ALZ) in patients with relapsing–remitting multiple sclerosis.MethodsPatients treated with AHSCT (n=69) received a conditioning regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulinerG (6.0 mg/kg). Patients treated with ALZ (n=75) received a dose of 60 mg over 5 days, a repeated dose of 36 mg over 3 days after 1 year and then as needed. Follow-up visits with assessment of the expanded disability status scale score, adverse events and MR investigations were made at least yearly.ResultsThe Kaplan-Meier estimates of the primary outcome measure ‘no evidence of disease activity’ was 88% for AHSCT and 37% for ALZ at 3 years, p<0.0001. The secondary endpoint of annualised relapse rate was 0.04 for AHSCT and 0.1 for ALZ, p=0.03. At last follow-up, the proportions of patients who improved, were stable or worsened were 57%/41%/1% (AHSCT) and 45%/43%/12% (ALZ), p=0.06 Adverse events grade three or higher were present in 48/69 patients treated with AHSCT and 0/75 treated with ALZ in the first 100 days after treatment initiation. The most common long-term adverse event was thyroid disease with Kaplan-Meier estimates at 3 years of 21% for AHSCT and 46% for ALZ, p=0.005.ConclusionsIn this observational cohort study, treatment with AHSCT was associated with a higher likelihood of maintaining ‘no evidence of disease activity’. Adverse events were more frequent with AHSCT in the first 100 days, but thereafter more common in patients treated with ALZ.

Autologous Hematopoietic Cell Transplant for Patients With Multiple Sclerosis

“…Of the 6 included primary studies, 2 were RCTs 16,17 and 4 were retrospective cohort studies. [18][19][20][21] Both RCTs (1 phase III 16 and 1 phase II 17 ) were open-label, multi-centre, parallel, 1:1 trials. Both reported sample size calculations to detect a clinically relevant treatment effect.…”

“…The detailed characteristics of the included primary studies [16][17][18][19][20][21] (Table 2) and the European Society for Blood and Marrow Transplantation (EBMT) guideline 12 and the American Society for Blood and Marrow Transplantation (ASBMT) 22 guideline (Table 3) are presented in Appendix 2.…”

Stem Cell Therapies for Progressive Multiple Sclerosis

“…On the recommendations of groups such as the (United States) National Multiple Sclerosis Society (Miller et al, 2021) and European Society for Blood and Marrow Transplantation (Sharrack et al, 2020), autologous HSCT may be beneficial for the treatment of active RRMS that is refractive to current DMTs (or in cases wherein these are contraindicated). Indeed, some appraisals suggests that HSCT may represent a cost-effective alternative to DMTs for the treatment of RRMS (Burt et al, 2020), however, larger studies are ongoing to ascertain whether HSCT is truly advantageous to current best standards of care [e.g., (Burt et al, 2019;Zhukovsky et al, 2021), and the BEAT-MS trial, NCT04047628]. While promising for the treatment of RRMS, the weight of clinical evidence suggests that autologous HSCT has limited efficacy in treating chronic PMS without superimposed disease activity (Bowen et al, 2012;Miller et al, 2021).…”

Made to Measure: Patient-Tailored Treatment of Multiple Sclerosis Using Cell-Based Therapies

“…The MS International Stem Cell Transplant (MIST)-trial (NCT00273364) demonstrated the superiority of AHSCT versus DMTs in terms of the time to disease progression [ 43 ]. More recently, an observational cohort study compared outcomes after treatment with alemtuzumab and AHSCT and found that the chance of maintaining NEDA was significantly higher in the AHSCT-treated group [ 44 ]. Several clinical trials, comparing the effects of AHSCT with high efficacy DMTs in patients with active RRMS, are ongoing ( Table 1 ).…”