STUDY: HSCT vs Alemtuzumab (Lemtrada)

[ActiveMSers]

Therapeutic strategies for aggressive multiple sclerosis: a single center experience with alemtuzumab and autologous hematopoietic stem cells transplantation

G. Boffa1, C. Lapucci1, E. Sbragia1, E. Capello1, D. Currò1, A. Laroni1, L. Roccatagliata2, A. Uccelli1, F. Gualandi3, G. Mancardi1, M. Inglese1 1Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, 2Department of Health Science (DISSAL), University of Genoa, Genoa, Italy/IRCCS AOU San Martino-IST, Genoa, Italy, 3Bone Marrow Transplantation Unit, San Martino Hospital, Genova, Italy, Genova, Italy

Background: 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 effects. However, experience is limited and uncertainty remains on correct patient selection.

Aims: To characterize and compare therapeutic strategies for aggressive MS in a real life single center experience.

Methods: 77 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 (mean age=33 (±7) years, median EDSS=6 (1-8,5), RRMS 74%, females 68%). 30 patients underwent treatment with alemtuzumab and 47 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 2 years.

Results: At baseline, aHSCT-treated patients showed higher ARR (p=0,02), worse EDSS (p< 0,001) and more pronounced MRI activity (number of Gd+ lesions at baseline, p< 0,001) than alemtuzumab treated patients. Proportion of patients achieving NEDA at 2 years was 78% and 70% for the aHSCT and alemtuzumab group, respectively. Relapses occurred more frequently in the alemtuzumab group (p=0,01), with no differences in EDSS at 2 years. Early adverse events were more frequent in the aHSCT group (p< 0,001). One death occurred in the aHSCT group, although the relation with the procedure is not clear. Late adverse events, especially autoimmune disorders were more frequent in the alemtuzumab group (p=0,04).

Conclusions: Alemtuzumab and aHSCT are effective treatment choices for aggressive MS, providing complete disease remission in a large proportion of patients at 2 years. aHSCT induces earlier disease remission compared to alemtuzumab.

[ActiveMSers]

This study found more benefit for aHSCT... -D

Efficacy of aHSCT and Alemtuzumab: A Case-Control Study in Hamburg MS-patients

V. Häußler1, J.-P. Stellmann1, J. Pöttgen1, C. Wolschke2, M.A. Friese1, C. Heesen1, N. Kröger2 1Institute of Neuroimmunology and Multiple Sclerosis, 2Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Introduction: Autologous stem cell transplantation (aHSCT) is increasingly recognized as a therapy in highly inflammatory multiple sclerosis (MS). Recently, a randomised-controlled trial showed promising results with no progression in relapsing-remitting MS in 98 % of the patients within the first 2 years after treatment. Alemtuzumab, one of the currently most effective approved therapies, reached a maximal proportion of progression free patients of 78% in the pivotal trial.

Objectives: To assess differences in disease activity in highly inflammatory MS patients treated with aHSCT or alemtuzumab.
Methods: We performed a prospective Case-Control-Study observing clinical course (EDSS and relapses), MRI parameters (new T2 lesions) and neuropsychological assessment in 40 patients with MS receiving either aHSCT or alemtuzumab between 2007 and 2018 at our centre. We used survival analyses to compare the primary outcome “No Evidence of disease activity” (NEDA) as defined by no EDSS progression, no relapse and no new T2 lesion on MRI.

Results: 19 patients, of which 12 showed relapsing-remitting MS and 7 progressive MS with on-going high inflammatory activity, were treated with aHSCT, whereas 5 of the 21 patients with alemtuzumab suffered from an underlying chronic disease course. There were no significant differences regarding disease course, sex (63%/66% female), age (mean(SD) 35.1(10.0)/37.9(9.9) years), EDSS (4.7(1.9)/4.9 (1.85)), or number of prior immunotherapies (2.3(1.2)/2.8(1.5)). However, disease duration was significantly longer in the alemtuzumab group (5.4 (4.2)/11.3(6.8) years) and relapse activity 2 years prior to the initiated therapy (1.8(2.0)/1.0(1.0)) tended to be lower. Follow-up time was 58.8 (36.0) months in the aHSCT group compared to 25.2(12.0) months in the alemtuzumab treated patients. We observed significantly more patients fulfilling NEDA in the aHSCT group (0.48/0.35, p = 0.048) compared to the alemtuzumab treated patients. Confirmed EDSS progression was not different between groups.

Conclusion: This case-control study suggests that aHSCT suppresses inflammatory activity in MS more effectively than alemtuzumab. Despite longer disease duration and lower pre-treatment relapse activity in the alemtuzumab group, which hypothetically should be associated with less inflammatory activity, more MRI activity and relapses were observed in this group in comparison to aHSCT treated patients.