Ibrutinib stopped working, what’s next

[Stacky66]

Morning all,a quick recap on journey so far, FCR treatment which kept things at bay for 14 months, then onto Ibrutinib for 6 years approximately, currently lymph nodes at 5cm , next treatment starts in January Rituximab and Ventoclax for 2 years, just wondering if there are any alternatives? Thanks all Merry Christmas and Happy New Year

[lankisterguy Volunteer]

Hi Stacky66,

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I've been where you are, and about to change from my 5th targeted therapy to my 6th.

IMO(no medical training)- the most popular and proven effective is obinutuzumab / Gazyva(ro) and venetoclax / Venclexta, but some health systems are still using rituximab / Rituxan with venetoclax. Either of those combinations seem far ahead of everything else that would be available.

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Since you seem to be resistant to the covalent BTKi family, only the PiK3 family like idelalisib/ Zydelig , non covalent BTK like pirtobrutinib / Japirka, and CAR-T are approved so far, but the results are less impressive than venetoclax. See: cllsociety.org/cll-medicine...

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Len

[Stacky66 in reply to lankisterguy]

Thank you

[Skyshark]

There is a trial of triple combo Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR). I think this is the best way to use non covalent Pirtobrutinib after progression on covalent BTKi. Pirtobrutinib is not approved yet. Evens chance of getting PVR and the other arm VR is what's on offer anyway.

Churchill Hospital, Oxford

Royal Marsden Hospital, Surrey

bepartofresearch.nihr.ac.uk...

[Stacky66 in reply to Skyshark]

Thank you

[Jm954 Administrator in reply to Skyshark]

Good trial 👍

[GeriGi]

I think obinatizamab with venetoclax is preferred treatment.

[Stacky66 in reply to GeriGi]

Thank you

[MovingForward4423]

There are trials for reversible BTK that overcome resistance seen in Ibrutinib and other non reversible BTK. May be worth doing some research on trials that may be available.

[Skyshark]

UK NICE has only approved VenO for NHS first line. VenR is approved for2nd/nth line.