To evaluate efficacy and safety of series of aggressive relapsing-remitting (RR) MS patients treated with aHSCT and alemtuzumab in a single Italian MS center and followed for 3 years.

Aggressive multiple sclerosis (MS) represents almost 10% of all MS cases. Treatment of these patients is challenging and optimal strategies have yet to be defined. Alemtuzumab and autologous hematopoietic stem cells transplantation (aHSCT) represent ideal candidates for managing aggressive MS because of their profound and immediate immune-ablative e?ects. However, experience is limited and uncertainty remains on correct patient selection.

61 patients with aggressive MS, according to the criteria of Rush et al. [CA Rush et al. Nat Rev Neurol 2015], were retrospectively collected from the MS center of Genova. 32 patients underwent treatment with alemtuzumab and 29 with aHSCT (conditioning regimen: carmustine/etoposide/ara-C/melphalan (BEAM) or cyclophosphamide). The proportion of patients with complete disease remission (no evidence of activity -NEDA-) was calculated at 3 years.

At baseline, aHSCT patients were younger than alemtuzumab patients (t=2.16; p=0.035), had higher EDSS (Mann-Whitney U=106; p<0.001) and more active MRI scans (Fisher exact test=12.63; p=0.001) with a higher number of baseline T1-gadolinium enhancing lesions (Mann-Whitney U=100; p<0.001). Proportion of patients achieving NEDA at 3 years was 70.8% and 46.1% for the aHSCT and alemtuzumab group, respectively. Relapses occurred more frequently in the alemtuzumab group (p<0,001). The interaction treatment x time in RM-ANCOVA showed a significant effect of aHSCT in promoting EDSS improvement compared with alemtuzumab (mean difference [95% CI]= 2,15 [1.24-3.05], p<0.001). Early adverse events were more frequent in the aHSCT group, while late adverse events, especially autoimmune disorders, were more frequent in the alemtuzumab group (p< 0,001).

Intense immunosuppression followed by aHSCT is superior to alemtuzumab in reducing relapses and MRI activity in aggressive MS and promotes disability improvement.