A recent consultation with a CLL specialist, and confirmation of genetic markers

[Sagarcanada]

My wife had an appointment with CLL specialist Dr. C. Chen yesterday. We also performed other blood tests. I had a pleasant consultation with Dr. Chen. I was perplexed because of the TP53 mutation, whether it was discovered or not. I posted an earlier post that she has a TP53 mutation. I am sorry for that.

The CLL specialist reports that the patient has: Rai stage 0 with trisomy 12,13q deletion and mutant IgHV. So no more TP53 mutations for her.

I hope this is better. She had her last consultation on March 21, 2024, and we discovered that her WBC and Lymphocyte counts had declined yesterday. On March 21, WBC was 137, but it dropped to 127 yesterday. Similarly, lymphocytes were 127 in March but dropped to 119 yesterday. I believe that is a good indication, but I am unable to comprehend why, therefore I am posting it to see what your experiences are.

Other parameters are nearly stable. I want to see your responses, CLLers. My respects go to this wonderful forum.

Regards

Sagar

[Bluesinthenight]

SugarCanada: Ideally, your wife's attending physician discussed what is currently known of the molecular abnormalities found in her CLL cells. The mutated IgHv is favorable in all studies of outcome and treatment. Trisomy 12 is common as is 13q deletion. Both found in early stage CLL and neither unfavorable prognostically. Absence of p53 mutation/deletion is favorable. That said, molecular markers - whether favorable or unfavorable - do not tell the whole story. Newer tests with greater sensitivity to detect markers and to find new prognostic markers are in development: Much is unknown. Her white count trend going lower on 3 values is good, but the changes are relatively small and could be do to chance alone given the inherent variability of all tests: the tests themselves, and the variation within each person. So, discuss these questions about marker and lab test significance with your wife's hematologist.

PS I have had un-mutated IgHv since my Dx in 2008 plus trisomy 12 and a mutation of SAM-HD1. I have been on a covalent binding BTK inhibitor for 12 years without the need to change to another class of drug. Unfavorable marker, but favorable course.

[Sagarcanada in reply to Bluesinthenight]

Dear Bluesinthenigh,

We have bi-monthly follow-up appointments at Princes Margaret Cancer Hospital in Toronto with Dr. Chen, a CLL specialist who also serves as our primary doctor. I wasn't sure if my wife had mutant TP53 a few days ago, but the test came back negative, which is positive. So far, my knowledge TP53 has some unfavorable indicators.

I think your present treatment approach is good. Could you tell me about your remission experiences with your medication?

Good luck with your CLL experience.

Regards

Sagar

[Bluesinthenight in reply to Sagarcanada]

With respect to the BTK inhibitors that I've been treated with, the standard is continuous therapy as long as it is tolerable, that is, no troublesome toxic effects, and no resistance to the treatment develops. I've had one treatment break because of numerous mouth and throat sores that were thought due to ibrutinib during my seventh year of treatment with it. But after 7 months off of treatment my blood counts decreased markedly and lymph nodes increased in size. I have never developed mutations of BTK, PKCg or other known mutations associated with BTK resistance, so I restarted treatment, this time with the newer BTK inhibitor, acalabrutinib (Calquence) and everything improved. I continue on that agent. Complete remission or "minimal residual disease" is uncommon on single agent BTK inhibitors. I personally would not favor stopping my treatment unless there again were troublesome side effects or another reason such as surgical procedure, or when I developed Covid a year ago and needed Paxlovid treatment that required brief discontinuation of the Calquence. I believe this approach remains the standard of care for single agent BTK treatment, at least with the currently available BTK inhibitors. So I regard "remission" while on single agent BTK inhibitor treatment as improvement and control of my CLL (i.e., adequate blood counts, no evidence of progression on scans or in bone marrow exam), but not eradication. I tolerate continuous acalabrutinib treatment very well.

I Hope this is helpful, Sagar.

[Sagarcanada in reply to Bluesinthenight]

Hello Bluesinthenight

Thank you for sharing your positive experiences from your CLL journey. I know you are in your seventh year of treatment. My understanding of the remission time was slightly different because I had a different impression. I assumed that if you were in remission, you didn't have to take medication. When the remission ends, you begin the second cycle of medicine. If I am wrong please correct me. I wish you good luck with your medication.

Regards

Sagar

[Bluesinthenight in reply to Sagarcanada]

No, remission does not imply stopping treatment. Even time-limited V+O therapy does not stop if uMRD is achieved before 24 months of therapy.

"Remission" can mean partial remission or improvement short of clearance of all evidence of leukemia. As mentioned before, for BTK inhibitors, the standard of care remains continuous therapy unless unacceptable toxicity, disease progression, or need for a temporary/short term interruption for surgery, or another treatment (e.g., covid treatment with paxlovid). The second generation BTK inhibitors acalabrutinib and zanabrutinib are better tolerated and therefore easier to continue long term compared to ibrutinib. The terms "remission" and "cycle" are important to understand. This is my take on these. I suggest you discuss them with your hematologist.

[Skyshark]

Well that is both good news and partly bad.

The negative for TP53 mutation is good.

The mutated IgHV is good for prognosis but in many Canadian provinces restricts the available range of first line treatments when needed.

People have entered trials with WBC up to 500. The need for treatment may depend on B symptoms.

[Sagarcanada in reply to Skyshark]

Dear Skyshark,

Thank you so much for the information.

We have not begun treatment yet, and my wife is still in the W&W state. We do not have any particular insurance for treatment. We live in Ontario and I'm not sure which drugs are restricted. We have regular follow-ups at Princes Margaret Cancer Hospital in Toronto, with Dr. Chen, a CLL specialist and our follow-up doctor.I'd still like to hear from you if you have any other information or experiences with this. Good luck with your treatment and your CLL journey.

Regards

Sagar

[AussieNeil Partner Administrator in reply to Sagarcanada]

Sagar,

The situation in Canada is gradually improving, so hopefully better choices will be available should the time for treatment arrive. You'll need to keep in mind that when new treatment options can be federally approved in Canada, it's then up to the provinces to allocated funding.

Neil

[Sagarcanada in reply to AussieNeil]

Dear AussieNeil,

Thank you so much for your response. I wish for the finest timing to arrive.

Regards

Sagar

[LeoPa]

Probably just normal fluctuations. The trend is important. You will see upon the next visit whether the numbers go lower or return back higher.

[Sagarcanada in reply to LeoPa]

Dear LeoPa,

I am eagerly awaiting our next checkup and blood work to see how the trend will progress. Regards

Sagar

[hazelton]

you have an excellent hematologist who is terrific at explaining things

[Sagarcanada in reply to hazelton]

Dear Hazelton,

I discovered Dr Chen through a referral from the CLL Society. She is excellent.

Regards

Sagar