Most people would agree that the alemtuzumab experience has been less that anticipated. We have seen unexpected deaths in some clinical trials and failure of response in patients with bulky disease. A paper in Haematologica addresses this.
They have studied pharmakokinetics in responders and non-responders and lo and behold the non-responders are under-dosed. Maximal concentration of alemtuzumab in responders was 1.69 micrograms per ml and in non-responders was 0.44 micrograms per ml.
I have previously written that the deaths from alemtuzumab, which occurred in an attempt to remove residual disease were caused by giving too large a dose too soon after FCR; I would venture to suggest that failure of bulky disease to respond is due to too small a dose being given. After all the original Lancet paper on Campath had responses in bulky disease.