New CML Agents - ASH notes, cont.

[Guest guest]

Hi Friends,

I¹m back to working on my ASH notes and summaries, though as I¹ll have

limited blocks of time for this over the next week or so, my reporting will

probably remain sporadic.

I thought I¹d be writing long reports on the two remaining ³Corporate Friday

Symposia² which I hadn¹t gotten around to summarizing previously, but after

reviewing Cheryl and Suzan¹s notes I find that I don¹t have that much to

add. One point that does stand out from me from the talk on ³New CML

Agents² by Kantarjian, Sawyers and Guilhot was the amount of

myelosuppression experienced in the Phase II trial of dasatinib (the BMS

drug): 100% of these patients became anemic, 96% experienced

thrombocytopenia (low platelets), which was moderate to severe (grade 3-4)

in 79%. The incidence of neutropenia (low white blood count) was also high,

though I failed to copy down the number.

Most of this toxicity occurred early in therapy and tended to improve over

time. Further, although myelosuppression was frequent and quite severe in

many, it¹s unlikely that patients treated earlier in their disease would

suffer the same consequences. All the Phase II patients had either failed IM

or were intolerant to it, and most of them had pretty advanced disease. So

as with IM in newly diagnosed CML patients, low cell counts can be largely

attributed to the killing of leukemic cells while few healthy normal

precursors remain to repopulate the marrow.

Still, it¹s my impression that marrow toxicity is worse with dasatinib than

with IM. This makes sense given that it inhibits two enzymes rather than

just BCR-ABL alone. I browsed through Jerry Mayfield¹s site to see if I

could shed more light on this, but was unsuccessful. Do any of you know how

dasatinib and IM toxicity (hematologic or otherwise) compare in patients

whose CML is not so advanced?

Best,

R