PCI-32765, CAL-101 & competition between CLL clones

January 10, 2011

Re: Re: FDA

At 01:03 PM 1/10/2011, Terry Hamblin MD wrote:

>I think you are missing Dr Furman's point. The new kinase inhibitors

>apparently produce benefit without a response.

Are such research results that demonstrate this (for PCI-32765 and/or

CAL-101) published in a scientific journal? or are they so far just

summarized in press releases?

At 01:03 PM 1/10/2011, Terry Hamblin MD wrote:

>Because there is a persisting lymphocytosis, the shrinkage of spleen

>and lymph nodes count for nothing. They are labelled as

>non-responders, yet potentially such patients may stabilize their

>disease for many years. Merely having CLL does not necessarily harm people.

Yes, just as many of the untreated W & W CLL patients have no harms

from having CLL.

The observations of benefit without response (e.g. continued

lymphocytosis), makes me wonder whether PCI-32765 and/or CAL-101 has

achieved what I had theorized (on 9/20/10) in a thread ( " competition

between CLL clones " ) related to chemo-resistant side-populations of

CLL cells ( " SP-CLL cells " , innate or chemo-induced) more rapidly

proliferating 'after' treatment with different chemo agents (see

PMID: 20827287).

Specifically, in that thread, I wondered whether there may be a

corollary to the observations, i.e.

" ....would it be possible to achieve a balance whereby one

therapeutically greatly reduces the pathological effects (e.g.

disruption of marrow production of normal blood cells) of the

dominant non-resistant CLL cells, yet maintains a population of those

non-resistant CLL cells sufficient to continue to effectively compete

against and, thus, keep at low levels the minority population of more

pathogenic SP-CLL cells? Effectively, this would be a strategy for

prolonging an indolent watch-and-wait phase for a patient. "

Could PCI-32765 and/or CAL-101 be such a W & W maintenance

therapy? and how long might such a maintenance therapy be effective

without significant pathological effects?

Al Janski

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