Short-term evaluation of alemtuzumab to ocrelizumab switch in MS patients with disease activity after alemtuzumab: An italian multicentric study

Background: the management of MS patients (pts) who show disease activity after 2 alemtuzumab (ALM) courses represents an unsolved issue No real-life data about the switch to ocrelizumab (OCR) have been reported yet Objectives: To describe efficacy and safety outcome of OCR patients switching from ALM due to persistence of disease activity after ALM Methods: MS pts who switched from ALM to OCR from March 2019 to March 2020 were retro- and prospectively recruited from different Italian MS Centers Clinical, immunological and neuroradiological data about ALM treatment period, ALM-OCR interval and OCR treatment period were collected Results: we recruited 23 MS pts [mean age: 35 7(SD±6 8);female, 40 1%;Relapsing Remitting, (RR): 75 8%, active Secondary progressive, (aSP): 24 2%;mean time interval (days) from II ALM course: 87 4(SD±108);cumulative number of relapses: 21;mean number of new T2 and Gd+ lesions: 4 1(SD±4 5) and 1 6(SD±3 1);median EDSS:3(range 1-7)] The mean follow-up (FU) from OCR start was 7 9±7 4 months Efficacy: 4 (17 4%) pts had a relapse after OCR start (1 pt relapsed between the first and the second OCR infusion and 3 pts after 3, 11 and 15 months from OCR start respectively), with complete recovery after steroid treatment 4 (17 4%) pts showed radiological activity with no clinical correlates at 3 months (n=2), 4 months (n=1) and 9 months (n=1) EDSS was stable except for 1 aSP patient who showed 1-year disability progression Safety: I) Infusion Associated Reactions (IARs) occurrence was significantly lower with respect to alemtuzumab courses (p<0 05);(ii) infections: mild upper airways (n=1), urinary infections (n=1), appendicectomy (n=1) and fever due to probable Sars-Cov2 infection (n=1) For 12 pts, data about immunophenotype were available Of them, no pts showed T CD4+ cell count decrease <200 cell/mm3 at 3, 6-months and 1-year FU;complete B CD19+ cell depletion (<5 cell/mm3) was confirmed at 3, 6-months and 1-year FU 10 (43 4%) pts developed hypogammaglobulinemia without developing associated infectious events C) Autoimmunity: no alemtuzumab-related new complications occurred Conclusions: short-term FU seems to suggest that the switch to OCR in MS patients who showed disease activity after 2 ALM courses is characterized by a good safety and efficacy profile, although clinical and neuroradiological activity can be detected both in an early and in a later phase of treatment Longer followup is warranted and recruitment is still ongoing