Thursday, October 27, 2011

More from Brooklyn- Kinase Inhibitors for CLL

Except maybe for a transplant, a cure for CLL is still not around the corner and is not likely going to be a single magic bullet. Progress is rapid and exciting, but clinical application is slow and very very expensive.

What is more likely is that a series of lower toxicity, higher specificity, more personalized therapy will be coming our way.

If we choose wisely, and are on the happy side of the survival curves AND meet the strict entry criteria for a trial (set up to insure approval of the drug and not to help the patients in the study) or the very limited FDA indications for our therapy (established among other reasons to give insurance companies coverage to say no to our needs) AND can afford the possible calamitous expenses of these new approaches either through insurance or our savings, we may be able to keep going for a long long time.

Some of the options include the new generation of small molecules that inhibit pathways that are preferentially expressed in CLL cells. Often these drugs block the cross talk (BCR) with other supporting cells, making the cancer clone more vulnerable.

I didn't see any data in Brooklyn, but I heard reassurance that these oral drugs like PCI 32765 (as the manufacturer's web site says: "As a Btk inhibitor, PCI-32765 blocks BCR signaling in human B cells but does not affect T cell receptor (TCR) signaling") and CAL 101 (a selective PI3 kinase inhibitor) and others in the pipeline not only shrink the nodes, but that the rise in the white count when the clonal cancer cells are run out the nodes is only temporary and it too falls to normal, AND even the bone marrow gets cleaned up.

Few side effects, but the risk of infection is significant and seems to me is a bit underplayed.

These drugs are going to big part of the future of CLL management, but now they are only available in trials, and it seems that you need to stay on them very long term or the leukemia quickly flares up again. Nodes can flare up again almost overnight to bigger than they were before therapy But the argument on the other side, is that if they are so safe, no worries, why not stay on them forever. The drug companies love this logic, but that is true with a ton of other therapies from insulin to blood pressure meds.

To their credit, the drug companies are allowing patients to continue (for free) on the meds after the trials are closed.

Not close to a cure, still they are a big step forward.

For that I am grateful.

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