In advice that I have been giving over the past 5 years I have been stressing that CD20 is brighter in patients who have trisomy 12. Indeed we noticed some time ago that trisomy 12 CLL was rather different from other types of CLL [1]. Today, published in the British journal of Haematology comes mathematical confirmation of our observation, from Michael Keating's group [2].
In patients with trisomy 12 there were 23,603 CD20 antigenic sites per cell compared with 10,781 for del 13q, 9,341 for del 17p, 8,828 for those with negative FISH and 5,886 for those with del 11q. The figures for trisomy 12 and del 11q patients were statistically significantly different.
Does this matter? Yes, because rituximab targets CD20. In the same paper the MDACC group report that the combination of rituximab and GM-CSF produced responses in93% of patients with trisomy 12, 73% in patients with negative FISH, del 13q or del 17p, and 50% in patients with del 11q.
References
1] Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients. Matutes E, Oscier D, Garcia-Marco-J, Ellis J, Copplestone A, Gillingham R, Hamblin T, Lens D, Swansbury GJ, Catovsky D. Brit J Haem 1996 92: 382-8
2] Chronic lymphocytic leukaemia CD20 expression is dependent on the genetic subtype: a study of quantitative flow cytometry and fluorescent in situ hybridization in 510 patients. Tam CS, Otero-Palacios J, Abruzzi LV et al. Brit J Haem 2008 141: 36-40.
3 comments:
Another outstanding bit of research that once you read it, you think, "well, of course!"
It does make a difference. Don't you think this eliminates or at least should cause people to rethink the use of R in 11q and 17p del?
Maybe a good first-line treatment (in addition to the ones you've favored over the years) would be HDMP+Campath in instances were 11q is present, but bulky nodes are not. R would just select out the non-11q or 17p cells, leaving the patient much worse off.
I wish someone had counted out the numbers a few years ago...
I wouldn't be as dismissive of rituximab as that. It still has some effect in low-density cases, but perhaps the newer anti-CD20s would be more appropriate.
Really, isn't rituximab a bust? Has it cured a single person? I don't think so.
It may lead to more complete remissions but as you are so found of pointing out, overall survival is unchanged.
Maybe these so-called second and third generation CD20 antibodies will be marginally better. Somehow, I don't think so.
The only cures in cancer are from chemotherapy, surgery and radiation, and that's only in certain cancers.
Traditional drugs such as fludarabine and your favorite, chlorambucil have not been supplanted with any other agent, as far as I know.
MD Anderson loves their FCR, but as you point out, they don't bother with phase III trials so we are all just left guessing.
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