Is it time to switch to acalabrutinib?

[suz02]

My WBC rose from 7.5 to 13.5 over the past few years, and I've been on ibrutinib for five years. Should i be worried. Should i try acalabrutinib?

[Hidden]

most likely resistance to ibrutinib would be mirrored by resistance to acalabrutinib.

venclexta or duvelsib monotherapy would likely be more effective-with or without a cd20 antibody

[AussieNeil Partner Administrator in reply to Hidden]

That's not necessarily the case. The newer BTK inhibitors bond to the BTK in a different manner and some, such as LOXO-305 have been shown to work when Ibrutinib resistance develops.

However I agree with you and Len that other drugs would likely be tried first if they were approved where you live. Suz, you first have to confirm resistance HAS developed.

Neil

[Hidden in reply to AussieNeil]

i thought ibrutinib intolerance was being allergic to ibrutinib. I saw no words about ibrutinib resistant.

[cajunjeff in reply to Hidden]

I agree. For people who are intolerant of ibrutinib, they might try acalabrutinib which supposedly has less side effects. But to my understanding, Ibrutinib and acalabrutinib are covalent binders, therefore I would think ibrutinib resistance would predict acalabrutinib resistance.

There are btk inhibitors being investigated now that bind non covalently. These drugs might well overcome ibrutinib resistance.

But insofar as acalabrutinib goes, I think it could overcome ibrutinib intolerance but probably not ibrutinib resistance.

[AussieNeil Partner Administrator in reply to cajunjeff]

You are both correct about Acalabrutinib bonding covalently and Ivotedfornixon is right about intolerance vs resistance (I'd just woken up and have corrected my reply). Another BTK inhibitor like LOXO-305 (currently available only in trials) might work, but first resistance needs to be confirmed. The raised WBC may well be due to a higher neutrophil and other WBC counts.

In the event of resistance being confirmed, the standard approach would be to switch to another class of drug.

Suz, with respect to BTK inhibitors, these posts may be of interest:

healthunlocked.com/cllsuppo...

healthunlocked.com/cllsuppo...

Neil

[tsvieps in reply to AussieNeil]

To Suz02: Per Neil, 13k WBC by itself certainly is not worrisome. Many other parameters must be looked at. This may not even be a long term trend. I have varied between 7k and 15k over the last 2 years; last week I was 10k.

If RBC is reasonable and Platelets etc are fine and general health is good, just keep monitoring and see if your oncologist has concerns about any trends.

[suz02 in reply to tsvieps]

Sounds good. Thank you for sharing -- it's reassuring.

[suz02 in reply to AussieNeil]

Great information! Thank you so much for sharing

[lankisterguy Volunteer]

Hi suz02,

-

It would be helpful if you tracked the two major components of your WBC, instead of the sum. Most of your WBC is normally from Neutrophils.

-

If your ANC/Neuts# is higher than normal causing the higher WBC total, then your CLL is probably NOT involved. It could indicate a bacterial or viral infection.

-

If the change in WBC is because of your ALC/Lymph# is several times normal range, then your CLL would be suspect.

_

You can find the normal lab values here:

cllsociety.org/toolbox/norm...

Neuts.# (ANC)Absolute Neutrophil Count1.70-7.00 x 10-9 /L

Lymphs# (ALC)Absolute Lymphocyte Count0.90-2.90 x 10-9 /L

-

I agree with Hidden that your CLL expert doctor would not likely suggest a BTK inhibitor (Acalabritnib/Calquence) that has the same activity, and the same resistance pathway as Ibrutinib.

But would likely add or switch you to a BCL inhibitor (Venetoclax/Venclexta) or a Pi3K inihibitor (Idelalisib/Zydelig or duvelisib/Copiktra en.wikipedia.org/wiki/Duvel... )

-

You really need to discuss these options with a CLL expert doctor to get the best choice.

-

Len

[suz02 in reply to lankisterguy]

This is GREAT information for me. Thank you so much...I'm looking at it, and a little dismayed none of my Dr.'s havent.