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.
5 comments:
Not a single word about toxicity though. Is it that much unexpected Terry that there is a dose-response effect with Alemtuzumab as with so many other agents?
I'm sure there is a dose effect on toxicity. Campath reacts but poorly with myelod precursors, but if all the lymphocytes are gone then it will damage the marrow. It will always go for T-cells though and T-cell precautions have to be taken.
Dr Terry...did I read once that the recipe for campath had changed over the years and that had some impact on its ability to fight big nodes or am I dreaming?...the breadth of your blog really continues to intrige and enlighten me...romanbob
Yes, there is a different way of making it now and it may affect glycosolation. I heard this at a meeting, but I haven't seen anything in print yet.
Interesting. Who would have guessed?
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