Effectiveness of Acalabrutinib dosage halved?

[Jevotchka]

Am trying to be rational but feeling very scared. Saw haematologist last week when several red flags were raised - weight loss , raised lymphocyte count, diarrhoea, increased fatigue, overheating at night (never had actual drenching night sweats not even with former breast cancer), greater anxiety and depression. Have been on Acalabrutnib as first line CLL treatment since 2019/2020 with no real issues until now. Have been taken off medication since last week and having various US/CT scans to rule out anything underlying before next visit to learn options for continuation of care plan. Was told last week that all above could be reaction now to Acalabrutinib and that an option, providing test results ok etc could be to halve dosage to 1 tablet a day. My question: is it quite common for those on Acalabrutinib to develop resistance and to have regular full dosage halved whilst continuing to offer better tolerated cll maintenance therapy with fewer side effects? And if taken off Acalabrutinib what alternatives have been offered? I am almost 73 and in London.

Apologies for rambling. Any advice or info on similar experiences and outcomes would be greatly appreciated.

[Jevotchka]

Thank you so much for your quick response. Will see if I can find out more.Wishing you well. 😀

[DRM18 in reply to Jevotchka]

Well, Zanubrutinib is the next-gen Acalabrutinib--different side effects, maybe fewer overall?--so if side effects are the problem, it's a good option, but ... if someone's resistant to Acalabrutinib (rather than intolerant of it), Zanu won't help, as it works the same way as Acala.

Pirtobrutinib works differently, though, and therefore is an option for those who are resistant to Acalabrutinib.

--Dave!

[Jevotchka in reply to DRM18]

Lol am doing something wrong as this my 5th attempt to say thank you for your reply to my query. GuessI will just have to wait until Wednesday to find out what comes next and hope for the best. Thank you again . All best wishes.

[SofiaDeo]

It sounds like there is a bit of miscommunication somewhere. If your symptoms (especially the lymphocyte count increase) are thought to be because *the acala is failing due to drug resistance*, the dose will not be halved. If the diarrhea is thought to be because of the drug, sometimes the dose will be decreased. But the weight loss, lymphocyte increase, and overheating (which is thought to be from cytokine release) seem more like symptoms that your CLL variant is actively growing again, becoming resistant to the drug. It's also possible these total symptoms are due to a GI infection of some sort. You are having additional testing to figure this out, and the scans are to see if internal lymph nodes are changing, is there a potential abcess, etc.

There are other option the UK uses when one drug fails, and there are clinical trials going on a number of sites. With you being in London, if there is a trial you/your doc thinks is promising, you probably won't be too far away from a trial site. Some of the trials are comparing currently approved drugs to see if one combination works better than another. Other trials are using drugs proven effective for other cancers and are now being tested for CLL, still others are brand new molecules.

[Jevotchka in reply to SofiaDeo]

Thank you so much for your detailed reply to my rather panic query. Am having next appointment this Wednesday so presume will know next steps then. It is hard to stay positive when scared and feeling alone even when not alone but your reply has helped . Thank you. All best wishes.

[CoachVera55]

I am 13.5yrs in with CLL before going to stage 4 & I am looking at Zanubrutinib. I have not had any previous treatment & my silly Onc suggested a clinical trial with multiple drugs. I want to start with oral & see how well tolerated & efficient that is because I do not do well with Western Medication. I can do whatever supplement that is known to help but even antibiotics & pain meds have the worst side effects for me. I know that there is research & breakthroughs being made daily. Don't worry just see what your doc has to say, best of luck!

[SofiaDeo in reply to CoachVera55]

There's some data coming out from the most recent ASH meeting that a *one year, time limited* treatment with 2 drugs is giving durable remissions. No taking a single BTK forever, no 2 year protocol with V&O, or triple drug regimens, just a single year of 2 agents. However, patients are needed to test this. So if a "one and done" seems attractive compared to being on a BTK like zanibrutinib indefinately, you may want to check it out.

And unfortunately for us, there doesn't seem to be a way to suss out what drugs cause problems ahead of time. It's not like some other disease states where drugs known to cause few side effects are initially tried, then "more toxic" ones are used, then the "most toxic" ones are finally tried. I get wanting to start with oral agents because IV can have more problems, but with CLL being so "patient specific", there's no way to say ahead of time if a BTK will give *you specifically* fewer side effects than Venclexta, with or without an anti CD20. And the same applies to how people are reacting to the anti CD20's: some have virtually zero effects, some have initial infusion problems only, still others stop after 3 or 4, others can do all 6. So IMO don't spend a great deal of time and get heavily invested considering *exactly* what treatment to start, in case you can't tolerate it. You may need to just try a few before finging one that works without giving side effects. This is good news IMO. We have choices, we no longer have to go through "set protocols" like some cancer patients do.

[Sewster in reply to SofiaDeo]

Exactly what meds are you referring to above? - “just a single year of 2 agents.”

My specialist as well as local hem/onc is recommending V &O for me; specialist is ok with me waiting longer before starting (my preference) and local hem/onc wants me to start NOW.

[SofiaDeo in reply to Sewster]

The initial study was V&Ibrutinib.. There now is a study looking at a single year of V&O compared against V&Acalabrutunib. So some people are still be followed on the V&I study, and there is a new study.

clinicaltrials.gov/ct2/show...

Ohio State University is also looking at A&V compared to A&O:

clinicaltrials.gov/ct2/show...

My understanding is that the O infusions are the standard 6, and any oral agents are for 1 year. So it's not necessarily "1 year of both" it's more "time limited treatment, and the entire course of therapy is a year" then one stops any meds. As opposed to continuous, single agent BTK.

My specialist is of the opinion that if one gets at least a 2 year uMRD status without disease growth, a repeat of previous treatment may be possible. At least some specialists are discussing this concept. So no drug resistance occurs, and the disease is "managed" as opposed to trying to "cure" it. If a patient doesn't have severe side effects, and resistance is prevented, why not just repeat the treatment? Unless something better/more specific/less toxic is found.

I am hoping to get at least 2 years this time around, and when mine comes back, just repeat V. I didn't react to it like I did to others, and the only other agent that gave me a good long remission was "more toxic", affecting B cells plus T cells. In today's environment, I am unwilling to affect both if I can help it!

[Jevotchka in reply to CoachVera55]

Thank you and to you too