New drug: MS-553 inhibitor for CLL/SLL who develop resistance to BTK inhibitors

[spi3]

MS-553 is a protein kinase C-beta (PKCß) inhibitor designed to be an alternative treatment option for patients with CLL/SLL who develop resistance to BTK inhibitors. Please see article at:

cllsociety.org/2023/02/ash-...

[DRM18]

Thanks for the link!

This drug is different from Pirtobrutinib?

[spi3 in reply to DRM18]

Great question but am not an expert on pirtobrutinib- maybe AussieNiel, Newdawn or CLLerinOz can answer?

[DRM18 in reply to spi3]

Apparently it's not the same as Pirtobrutinib, which is good news:

onclive.com/view/davids-hig...

[AussieNeil Administrator in reply to spi3]

 DRM18 and spi3,

Pirtobrutinib is a third generation Brutom's Tyrosine Kinase Inhibitor, or BTKi, (hence the 'brutinib' suffix). It has less off target effects seen with the second generation BTKi drugs, plus it bonds non-covalently, so when resistance develops with a first or second generation BTKi, (ibrutinib, acalabrutinib and zanubrutinib for example), it's possible to switch to pirtobrutinib and maintain CLL inhibition for a while longer.

If MS-553 becomes approved, this will be a much needed new class of inhibitor - "a protein kinase C-beta (PKCß) inhibitor". Whether it will be found to work well enough on its own or in combination with other approved CLL treatment protocols, is being determined in the study reported on in the CLL Society ASH2022 update spi3 provided: cllsociety.org/2023/02/ash-...

Thanks spi3, I've added MS-553 to the list of other drug classes in my reply to this post healthunlocked.com/cllsuppo...

Neil

[spi3 in reply to AussieNeil]

I knew you would have the answer - you and the Administrators are the best! Thank you so much

[bennevisplace]

Well spotted, go to the top of the class!

[Dahlia7]

The drug is actually MS-553. and not 533. The article goes back and forth with the number. I know because I’ve been on it for 7 cycles. Thanks for reporting and I just wanted to set the record straight so members can research it properly. Tony

[spi3 in reply to Dahlia7]

Thank you for the clarification. I praying you have success on it too

[Gradyboy in reply to Dahlia7]

How are you doing and feeling on this med?

[spi3 in reply to Gradyboy]

Dahlia7 is on the medication

[Dahlia7 in reply to Gradyboy]

I’m doing fairly well. It’s a lot slower to work than the other treatments I’ve had. It is a twice a day drug and has had more GI side effects for me than the other treatments. Therefore the protocol does require a dose escalation to mitigate the side effects. I’ve developed peripheral neuropathy while taking it and am trying a dose reduction to see if it helps. It may or may not be a side effect of the drug. I am feeling much better than when I started and required 4 blood transfusions and platelets so I’m pleased overall but the neuropathy is obviously problematic going forward. Thanks for asking. Tony

[spi3 in reply to Dahlia7]

I'm so glad you are doing better!

[AussieNeil Administrator in reply to Dahlia7]

Thanks for clarifying the number is MS-553. I did have it noted in my YABTKI post from August last year, where I noted "As of June 20, 2022, a total of 45 patients (median age 69; range 38-82) have been treated with at least one dose of therapy." That number perhaps includes you

[Dahlia7 in reply to AussieNeil]

I believe it does Neil. Thanks for all you do for us. Tony

[Dahlia7]

Thank you.

[Gradyboy in reply to Dahlia7]

How are you doing on this treatment?