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

[Guest guest]

The data for PCI-32765 and CAL-101 have only been reported in oral sessions at

meetings.

> >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

>

[Guest guest]

Re: Re: FDA

At 03:54 PM 1/10/2011, Rick Furman, MD wrote:

>These are agents that are demonstrating remarkable effects in

>patients with refractory disease.

Refractory CLL patients are predicted to have a higher proportion of

chemo-resistant side-populations of CLL cells ( " SP-CLL cells " ) than

untreated CLL patients, yet benefits, despite continued

lymphocytosis, were observed in refractory patients. How long those

benefits endure (with or without maintenance therapy with PCI-32765

or CAL-101) will be interesting.

Whatever the duration of benefits in refractory patients, one might

expect those benefits from these agents would endure longer in

previously untreated CLL patients, who should, on-average, have lower

levels of SP-CLL cells, and thus less probability of existence of CLL

clones that have mechanisms for resistance to these agents.

Are there yet any scheduled trials for testing these agents in

untreated CLL patients?

Al Janski

REFERENCE:

B-chronic lymphocytic leukemia chemoresistance involves innate and

acquired leukemic side population cells.

Leukemia advance online publication, 9 September 2010;

doi:10.1038/leu.2010.176.

PMID: 20827287