acalabrutinib stopped working. Can switching to venclexta help?

[Belkin123]

I am on acalabrutinib for two years. In first year my wbc went down from 150k to 18k, and for the second year from from 18k to 14k. My hgb is 15, plt 200k. My spleen decreased in size from 21cm to 14cm. I feel generally better, and no side effects. My dr think about switching to venclexta. I am scared of new treatment and possible side effects. I would like to hear the opinion of our wonderful community. Thank you all.

[lankisterguy Volunteer]

Hi Belkin123,

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I've been in your situation several times- you can see my treatment history here:

healthunlocked.com/user/lan...

I was on Venetoclax for the last 6 years with almost no side effects and started Calquence in January 2022 and stopped Venetoclax yesterday.

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I believe that most CLL expert doctors would suggest Venetoclax / Venclexta for your next treatment. The only question is whether to start the Venetoclax overlapping with your Acalabrutinib / Calquence or to stop all CLL treatments and wait until you progress to needing your next round of treatment.

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The advantage of overlapping is that you will be low risk for TLS and likely will not need to be hospitalized for the first two weeks of dose ramp up. And there are some theories that the BTKi treatments like Acalabrutinib have a synergistic effect on T-cells.

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Venetoclax has a history of some side effects, but like Acalabrutinib, 80% of patients have minimal problems and some of the 20% remainder have transient side effects that are treatable or resolve over time. It is very difficult to predict what, if any side effects you might encounter, but working closely with your CLL expert doctor is essential.

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Len

[whmk]

Why does your doctor believe that Acala is no longer working for you? Your numbers seem to be trending better (albeit slower) and there is no evidence that your CLL is progressing again.

[Belkin123 in reply to whmk]

I think my dr is looking for a tendency, it is obvious, that it does slow down. He is monitoring closely not to miss the point when wbc might go up. Thanks for your reply.

[lindalou5 in reply to Belkin123]

My numbers have gone steadily down, and then there is a hic-up where there is little improvement, but was told by specialist that there are times when the medicine works slower. I have been on Acal for almost three years (had a relapse a year ago-resumed treatment) and am still above 100,000.but still going down each visit. Hopefully it continues, even though it is slow, it is progress. When I hear of folks on here who have had theirs go down so fast, it makes me a bit nervous, but will stay the course as long as it has some improvement.

[Belkin123 in reply to lindalou5]

Dear Linda, I have read your story. It is not an easy one. Those markers make a big difference. So as long as you are getting a little better with meds, continue and be happy, that it is not getting worse. Regarding having a cat- it is a big dilemma for me too. I had cats all my life, but now I am not sure that I can take care of them. It is a big responsibility, when you live alone and have to go to a hospital. It is also a problem when they got sick. My last one died 10 years ago and I still did not get over it. Take care .

[whmk]

Every CLL drug seems to work well for 3-5 years before they stop working well. My philosophy is to let every drug work for 3-5 years until they stop working and then try another. Every 3-5 years scientists seem to be able to find a new and better drug so I will switch then and never have to worry about CLL progression.

[AussieNeil Partner Administrator in reply to whmk]

You are broadly right about the need to switch to a new line of therapy when a current therapy stops working. That's why CLL is still considered incurable. Thankfully we have never had so many treatment options as we have now, with many more on the way, per this post:healthunlocked.com/cllsuppo...

Your 3 - 5 year range for a treatment is, however a big simplification. It's a continuum, from (sadly) months for some treatments, to decades for others. Researchers are currently working out who will do well on a fixed term treatment and who will do better on a maintenance protocol. We know that about 55% of IGHV mutated folk do incredibly well on FCR, with early trial participants now starting their third decade in remission. Sadly sometimes IGHV unmutated folk only managed a few months remission after FCR or BR, but targeted therapies have significantly eliminated the disparity.

The RESONATE-2 first line ibrutinib vs chlorambucil clinical trial of 269 patients cancernetwork.com/view/surv... reported "Overall, with up to 7 years of follow-up, the median PFS for patients in the ibrutinib arm was not reached (HR, 0.160; 95% CI. 0.111-0.230), equating to an 84% reduction in the risk of progression or death." We have early ibrutinib trial participants entering their second decade of maintenance of their CLL. A significant percentage of those dropping out, did so because they couldn't tolerate the side effects. Second and third generation BTKi drugs have made big reductions in the severity of those side effects, so we should see even longer median progression free survival times with these new drugs.

Combination therapies can be successfully repeated; hitting the CLL multiple ways reduces the incidence of refractoriness developing.

Neil

[whmk in reply to AussieNeil]

Thanks for your more complete and nuanced answer. My main point is that it seems ill-advised to switch drugs before necessary because one might reach drug resistance/ineffectiveness on a larger set of potential solutions and a real need to switch due to progression.

[AussieNeil Partner Administrator in reply to whmk]

Indeed, we are finding that when resistance begins developing with targeted therapies such as BTKi drugs and venetoclax, it's best to stay on the failing drug until you start the next treatment. That seems to lessen the risk of tumour flare happening.

Neil

[Belkin123 in reply to AussieNeil]

Thank you so much Neil, for your response. I hope that I can stay on acalabrutinib a little longer till it stops working. I have a wonderful dr. Choi at UCSD. He is monitoring me closely. And thanks for all the responses from our community.

[AnneHill in reply to AussieNeil]

I am about to take Ibrutinib 120mg and although it was my decision I am nervous.I have been taking Ibrutinib for 3 years. I quickly achieved remission and for 7 months have been taking 240 mg with no change to my numbers.

I am hoping the muscle and joint pain improves but is the lower dose likely to cause resistance? Anne uk

[AussieNeil Partner Administrator in reply to AnneHill]

Theoretically there's a risk that a lower dose of ibrutinib could leave some CLL cells uninhibited, so that they could resume cloning. Any sub-clones with resistance to ibrutinib would have a selective advantage and eventually become dominant, so you'd see your lymphocyte count begin to rise again. Given your numbers are stable, there are probably very few CLL cells around needing inhibiting. Given how well you responded, perhaps you have even reached uMRD? I find it frustrating that there have been several trials checking how patients do on a reduced dose of ibrutinib, but they didn't report patient weight!

By the way I think you meant 280mg and 140mg (2 or 1 ibrutinib capsules per day).

Neil

[AnneHill in reply to AussieNeil]

Yes I meant 140mg. I was hoping I had reached uMRD. Optimistic I suppose.I have 2 weeks of 280mg remaining and I think I should use them or they will go to waste. The consultant will have a different start date though.

I have had telephone consultations for a long time and the next one will be in 3 months time. I will ask for a face to face if I am worried. Anne uk

[The-Man-with-a-Plan in reply to AussieNeil]

Neil. I always read your posts with great interest. Have you ever thought about going to Medical School? TMwaP

[HopeME in reply to The-Man-with-a-Plan]

Neil is retired and spends a lot of time working pro bono on Health Unlocked. I’m guessing, but I don’t think he has the time to teach at a Medical School.

Best,

Mark

[The-Man-with-a-Plan in reply to HopeME]

Hope:

I was half kidding.

That said, his CLL knowledgebase is on par with many of the medical experts who treat the disease. More importantly, his writings exude the patience and caring kindness of an outstanding teacher.

IF he were a physician, I believe his bedside manner would comfort many.

TMwaP

[Belkin123 in reply to AnneHill]

Thank you. I wish you to continue to do well.

[emmiekay]

Definitely give it a try. I had good luck with Venclexta (Venetoclax). Was easier on me than the bendamustine/Rituxan treatment.

[Belkin123]

Thanks. I wish you to continue to do well.

[Vizilo]

Somewhat similar to you, 18 months in on Acalabrutinib, most of my numbers are nearing normal except for WBC which is stuck in the 20K range. My spleen size is 13 cm which is on the high side of normal. My cll specialist is concerned that Acalabrutinib is nor working effectively. At my regular June visit, he suggested low dosage spleen irradiation to reduce the spleen size even more and to try to give Acalabrutinib a boost.

I underwent 6 doses of radiation a month ago (no side effects) and will find out it’s impact at my next cll specialist visit in about 6 weeks time.

When I asked him about switching to Venetoclax, he thought it was too early and he was hoping the spleen irradiation might give years more to Acalabrutinib effectiveness.

I will post results of my latest blood work in September. Here’s hoping the radiation has worked to further reduce my WBC.

[Belkin123 in reply to Vizilo]

It is very interesting. Where are you treated? Did anybody else went through radiation treatment? Please post your after treatment results. I wish you steady recovery..

[Vizilo in reply to Belkin123]

As I understand it, my cll specialist has treated a number of acalabrutinib “slow responders” with low dosage spleen radiation. Anecdotically, he has found that it has improved the effectiveness of acalabrutinib. As he explains, splenic radiation was used decades ago as a palliative treatment (to reduce the size of the spleen) when there were few cll treatments available. It went out of fashion and is now being investigated again as an add-on to targeted therapies.

I am hopeful it helps and will post my blood results in September. Thank you for your good wishes.

[Belkin123 in reply to Vizilo]

Thank you for your response. Yes, a lot of tumors were treated with local irradiation before. So, it might be helping with spleen as well. Thank you for sharing. I will wait for your updates. Wishing you the best outcome.

[Hiker13]

In June I completed the one year treatment plan of OV. It was an easy journey. A blood flow cytometry showed no cancer cells in my blood.

[Belkin123 in reply to Hiker13]

I wish you a long remission.

[Belkin123]

Yes, it is the same. I wish your brother to stay well.

[Denisguay]

What is WBC?

[AussieNeil Partner Administrator in reply to Denisguay]

White blood cells, that is neutrophils, lymphocytes, eosinophils, monocytes and basophils, which fight infections.

List of abbreviations:

healthunlocked.com/cllsuppo...