Acute effects of alemtuzumab infusion in patients with active relapsing-remitting MS

Abstract

Objective:Alemtuzumab exerts its clinical efficacy by its specific pattern of depletion and repopulation of different immune cells. Beyond long-term immunologic and clinical data, little is known about acute changes in immunologic and routine laboratory parameters and their clinical relevance during the initial alemtuzumab infusion.Methods:Fifteen patients with highly active MS were recruited. In addition to parameters including heart rate, blood pressure, body temperature, and monitoring of adverse events, complete blood cell count, liver enzymes, kidney function, acute-phase proteins, serum cytokine profile, complement activation, peripheral immune cell distribution, and their potential of cytokine release were investigated prior to and after methylprednisolone and after alemtuzumab on each day of alemtuzumab infusion.Results:After the first alemtuzumab infusion, both the total leukocyte and granulocyte counts markedly increased, whereas lymphocyte counts dramatically decreased. In addition to lymphocyte depletion, cell subtypes important for innate immunity also decreased within the first week after alemtuzumab infusion. Although patients reported feeling well, C-reactive protein and procalcitonin peaked at serum levels consistent with septic conditions. Increases in liver enzymes were detected, although kidney function remained stable. Proinflammatory serum cytokine levels clearly rose after the first alemtuzumab infusion. Alemtuzumab led to impaired cytokine release ex vivo in nondepleted cells. Normal clinical parameters and mild adverse events were presented.Conclusions:Dramatic immunologic effects were observed. Standardized infusion procedure and pretreatment management attenuated infusion-related reactions. Alemtuzumab-mediated effects led to artificially altered parameters in standard blood testing. We recommend clinical decision-making based on primarily clinical symptoms within the first alemtuzumab treatment week.

Hands on Alemtuzumab-experience from clinical practice: whom and how to treat

“…It is expressed on the surface of T-and B-cells and other cell populations but not on the hematological precursors [8]. Alemtuzumab infusion results in rapid depletion of the CD52 positive cells [9], leading to lymphopenia, which lasts for several years [10]. While B-cells recover relatively quickly within a range of 3-8 months, the repopulation of T cells occurs more slowly, as it needs up to 3 years and in another study up to 60 months for CD4+ and 30 months for CD8+ T cells in average [11,12].…”

“…The disadvantage is that the use of other treatment approaches after Alemtuzumab is more complicated due to the effects of irreversible depletion and repopulation, on the other side patient is practically off treatment after the second Alemtuzumab infusion. The rapid onset of Alemtuzumab treatment effects can be explained by depletion of both cells of the acquired and innate immune system, including the impairment in activation as well as cytokine release [9].…”

“…The highest drug level is reached after the last infusion [53]. However, even if this falls in the next few days, its effect with regard to lymphocyte depletion goes on, so that it is still possible to experience reactions related to cells depletion [9]. …”

“…But laboratory monitoring during infusion therapy is not needed, and it can even be affected by cell depletionrelated artifacts [9]. During the the first infusion week, rapid cellular depletion and impairment of activation of different adaptive and innate immune cell subtypes take place accompanied by marked serum cytokine increases.…”

“…Furthermore, transient elevation of liver enzymes, thrombocytopenia, and TSH modulation are demonstrated. So we recommend clinicians to be aware of clinical symptoms and vital data to initiate supportive analysis rather than standard laboratory testing within the first alemtuzumab treatment week [9].…”