Alemtuzumab in multiple sclerosis: A retrospective analysis of occult hemorrhagic magnetic resonance imaging lesions and risk factors

Abstract

Background and purpose Alemtuzumab, a monoclonal CD52 antibody, is a high‐efficacy disease‐modifying‐therapy in relapsing‐remitting multiple sclerosis (RRMS). Recently, intracerebral hemorrhage (ICH) was reported as a possible treatment‐related adverse event. Arterial hypertension during infusion was suggested as a potential cause, although platelet or endothelial dysfunction may also contribute. This study aimed to screen for occult hemorrhagic cerebral lesions after alemtuzumab treatment and to further elucidate risk factors. Methods We included 30 RRMS patients who received alemtuzumab treatment at Ghent University Hospital or Sint‐Jan Bruges Hospital. Retrospective data concerning vital signs, adverse effects and thrombocyte levels during treatment were collected. The occurrence of occult intracranial hemorrhagic lesions was assessed by magnetic resonance imaging with susceptibility‐weighted imaging (SWI). Results The mean (standard deviation [SD]) systolic blood pressure (SBP) during the morning, afternoon and evening was 120 (3.38) mmHg during first administration and 114 (4.40) mmHg during second administration (N = 13). There was no significant increase in SBP when comparing morning, afternoon and evening per day, nor was there a significant difference in daily mean SBP between consecutive administration days. Thrombocyte count during treatment cycles ranged between 107 × 109/L and 398 × 109/L, with a mean (SD) absolute reduction of 59.3 × 109/L (50.65) or a mean (SD) relative reduction of 25.0 (12.84)% (N = 20). No patient had ICH, nor did SWI show any cerebral microbleeds or other hemorrhagic lesions post‐treatment (N = 23). Conclusions In our patient population, alemtuzumab treatment was not associated with arterial hypertension, ICH or occult microbleeds. Possible differences in administration regimen (ambulatory vs. in‐hospital setting) and patient population (cardiovascular risk) might explain an increased risk in different populations.

Alemtuzumab induced hemodynamic change in relapsing multiple sclerosis occurs independent of corticosteroid premedication – a retrospective multicentre study

“…However, a similar mean change of SBP (≤8 mmHg) was found in a further study on day 3 to 5 of ATZ infusion (Chinea et al, 2020). In contrast to our results, another study (n = 30) that analysed occult haemorrhagic lesions on cerebral MRI did not find an increase of SBP in a subgroup of 13 patients neither in mornings, afternoons, or evenings nor across different days of administration (Bachmann et al, 2021). In this small retrospective study, also no signs of silent hemorrhagic lesions were detected on cerebral MRI.…”

Acute infusion effects in relapsing multiple sclerosis patients receiving alemtuzumab under a modified prophylaxis regimen

“…A recent report by Bachmann et al has also explored lower dose methylprednisone (500mg; all infusion days) (Bachmann et al, 2021). Like these authors, but in contrast to others such as Shosha et al (2021) we observed no consistent change in mean SBP over time on any infusion day.…”

Risk of secondary immune thrombocytopenia following alemtuzumab treatment for multiple sclerosis: a systematic review and meta-analysis

“…In the included studies, Bachmann H et al suggested that the thrombocytopenia related was not associated with ALZ intervention ( 24 ). However, they noted in their study that twenty out of thirty patients experienced mild or moderate reductions in platelet levels, all of which occurred during the first treatment cycle, and no bleeding symptoms were observed.…”

“…It is worth noting that this phenomenon occurred more than once. In all the included literature, three studies reported transient and temporary decreases in platelet levels, which returned to normal without intervention, and this accounted for a significant proportion ( 6 , 24 , 30 ). This is an intriguing observation that reminds us that ALZ may have a more pronounced interference with platelets and prompts us to consider the pathological mechanisms of ALZ treatment.…”