Flair trial. Report from the field.

[romarin]

Flair trial. Report from the field.

Hb118

White count 261.

Neutrophils 2.87

Lymphocytes 239

Platelets 127

I began taking Ibrutinib (along with Allopurinol for kidney support for a month only) 2 weeks ago, Nov 2nd. and began Rituximab the next day. This was divided into two stages, gentle the first day because my lymphocyte count was so high. Went fine, though I was nervous of course. Developed a headache during first infusion, and dreadful backache due to the too soft hospital bed! Averted this the following day with yoga mat and cushion and was fortunate enough to be assigned a bed with enough corner floor space to sit comfortably, for a while. Backache problem solved. (And I took herb tea bags this time.)

Since then I have noticed the lymph node in my neck diminish. (I now ask myself would I have presented with what’s left.) I have a mild spotty red rash on arms and body but no itching for now but I am bruising very easily. I think I am more tired than before, when I was suffering from significant restricting fatigue. Basically I am hibernating, following intensive nesting. (Not sure that is in the natural order of things...) But in general so far so good. (Not holding my breath however...) And I have had a few days of feeling very low - meditation helps for sure. But then those are the days you can't be bothered, just when you need it most.

Two week visit to clinic today confirms that my blood levels have increased slightly, as predicted, which would explain side effects.

[Cammie]

Romarin

All looks good apart from white count and lmphs but as you say this is expected as the Ibrutinib forces the cells from your nodes!

Keep up the good work!

Geoff

[romarin in reply to Cammie]

Thanks for helpful explanation - the cells being forced from the nodes into the blood. I would really like more description of the drug and process in tolerably plain English - any suggestions?!

[Cammie in reply to romarin]

Neil ?

[AussieNeil Administrator in reply to romarin]

Kinases comprise a group of enzymes (special proteins that speed up biochemical processes) that facilitate signalling within cells. Some of these (Bruton's tyrosine kinase (BTK), and the Phosphoinositide 3-kinases PI3K-γ and PI3K-δ (i.e. gamma and delta forms) are more commonly found in immune cells, in particular the B-lymphocyte and most importantly they have a key role in the B-cell receptor (BCR) stimulation. So they are a good targets for inhibitor drugs. Find a drug e.g. Ibrutinib, Idelalisib or Duvelisib that binds to these enzymes in the B-lymphocyte and you'll stop the BCR stimulation that keeps the cell alive. With the stimulation blocked, existing mechanisms within the cell are invoked that cause the cell to die in a controlled way (apoptosis).

If some of the kinases in some CLL cells aren't made correctly, then the inhibitor drugs may not bind. (These incorrectly made kinase versions may already be present, or could arise over time due to DNA copying errors creeping in.) Over time, CLL cells with non-binding kinase versions become dominant as the others die off and the patient will see an end to their remission. That can be countered by switching to a different kinase inhibitor or by using another drug that kills off CLL cells via an independent mechanism, which will target the CLL cells immune to the kinase inhibitor. Hence the FLAIR trial where Rituximab targets the CD20 on the CLL cell surface in combination with Ibrutinib, which turns off the BCR signalling inside the CLL cell.

Ibrutinib (Imbruvica) blocks BTK

Idelalisib (Zydelig) only blocks the p110δ isoform of PI3K

Duvelisib is a delta/gamma PI3K inhibitor; it blocks both the PI3K-δ and -γ isoforms

The (non marketing/trade) names actually tell you what these drugs do:

Ib/inib - Inhibit

brut - Brutons kinase

is - Isoform

dela - Delta

Du - Two

Neil

[romarin]

Many thanks for this explanation.