Is it time for treatment?

[Sagarcanada]

After a long absence, I am posting again about my wife's CLL progress. I am a caregiver; I am not a medical professional. My wife's genetic markers—trisomy 12, 13q deletion, and mutant IGHV—indicate an intermediate prognosis. Her complete blood count (CBC), however, exhibits rapidly shifting as follows:

• On January 20, the Hemoglblin was 105 g/L; on March 24, it is 99 g/L.

• On January 20, the WBC was 171 10*9 /L; on March 24, it is 210 10*9 /L

• On January 20, the RBC was 3.9210*12/L; on March 24, it is 3.57 10*12/L

As of 2020, my wife is at the W&W stage. At Princess Margaret Cancer Center, we had a pleasant conversation with Dr. Chen, and Physision mentioned that she might require treatment shortly. I also want to pay attention to fellow CLLs who have used this marker.

[cajunjeff]

Hello Sagarcanada. Of course her doctor knows the best answer, but i will give you a lay person educated guess as to whether it’s time for your wife to treat. I would say yes and no, that an argument can be made either way.

On the yes side, her hemoglobin is under 10. That fact, in and of itself, meets one of the criteria’s to begin treatment.

On the no side, if she is not meeting any other treatment criteria but for hemoglobin, and her hemoglobin is the tiniest bit out of range, an argument can be made to just monitor her and see how long she stays relatively stable. Its not like someone who has hemoglobin at 101 one day needs no treatment at all, and if they are at 99 the next day they needs to immediately start, treatment.

I think on a close call like this, the patient’s input should give great weight to the decision. If she has not been feeling well, or is tired of watch and waiting, she may want to get the treatment show on the road. Some will argue with the new meds, treating earlier might improve survival.

On the other hand, if she is feeling well, not having any b-symptoms, and in no rush to treat, I think that might influence the decision. As much as we hate watch and waiting, it’s still the standard and for good cause. While we watch and wait, new and better drugs keep coming out. The earlier we start, the earlier we likely see drug resistance. And until new data come out, the current data is that treating early does not improve overall survival.

Good doctors use the guidelines as guidelines, not hard and fast rules. Deciding the exact best moment to treat is an art, not a science. I doubt it makes much difference in her outcome if she starts now or six months from now. I personally would just have my doctor walk me through his thinking and go along with his recommendation, so long as his reasoning seems reasonable. Good luck to her. I have been treating 7 yrs now and feeling just fine.

[Sagarcanada in reply to cajunjeff]

I appreciate you sharing your CLL experiences, Cajunjeff. She is still working, but the doctor says she probably needs therapy sooner because she is tired and has nodes in her body. May 26 is the next appointment; let's see how the CLL progresses.

[AussieNeil Partner Administrator]

Since your wife's haemoglobin has dropped below 100, she meets an important trigger for starting treatment for her CLL. In Australia, packed red blood cell transfusions are given to maintain haemoglobin above 80, so the trigger for treatment with haemoglobin falling under 100 provides a buffer to allow for the impact of treatment drugs on the bone marrow while hopefully avoiding the need for supportive transfusions. If CLL bone marrow infiltration is quickly increasing (can be indicated by falling red blood, platelet and white blood cell counts other than lymphocytes), then the need for RBC transfusions to prevent organ damage from oxygen starvation is more likely.

When was your last conversation with Dr Chen? With that significant (10%) drop in your wife's RBC from 3.92 to 3.57 as well as the 6% drop in haemoglobin below 100 in the last 3 months, I'd personally be concerned at further delaying the start of treatment. That's because my haemoglobin dropped to 105 prior to my treatment (my RBC was just barely lower than your wife's at 3.43) and I needed a couple of red blood cell transfusions in my first month of treatment. The good news was that after A+V+O treatment, my haemoglobin improved to higher than it had been prior to my diagnosis - the best in nearly 15 years.

Your wife has done well to last in watch and wait until non-chemo options were finally available in Canada. That should be a big relief to you both, given the now proven much better outcomes from targeted therapies.

Neil

[Sagarcanada in reply to AussieNeil]

Thank you AussieNeil,

Your response is always a great lesson for our CLL journey. The last appointment was on January 20 and in between today and Jan 20 there has been a sharp decline.

All the best.

[AussieNeil Partner Administrator in reply to Sagarcanada]

It's that sharp decline which concerns me for your wife. May 26 may not seem far away given it's only 2 months from now, but if your wife's doctor doesn't want to see her until then, I would strongly recommend pushing for another blood test in a month.

Why? Well at diagnosis, CLL bone marrow infiltration is typically around 25 to 30%. By the time falling blood counts trigger the need for treatment, it can be around 90%. Your wife was diagnosed a bit over 4 years ago, so her bone marrow infiltration might be increasing by roughly 1% per month. If her bone marrow infiltration is around 90%, waiting another month could mean a further loss of 10% of her bone marrow production capacity. These are guesstimates, but illustrate why you can get a sharp decline when bone marrow capacity increases above 90% and why there's an optimum treatment window. 1% loss in a month at say 50% infiltration is only a 2% reduction, compared to 10% reduction at 90% infiltration.

My treatment start was delayed because I opted for a clinical trial to give me a 2 in 3 chance of being treated with targeted therapy, rather than FCR, a now largely replaced chemoimmunotherapy in Australia Canada, the USA and UK and a growing number of other countries. My trial was on hold for a month, then I had to wait another month for overseas blood testing, to check I met the acceptance criteria. In that 2 months, my haemoglobin dropped from 112 to 105, with one bounce to 119. In retrospect, I feel I could have had a far easier start to treatment if I had commenced earlier.

Neil

[Sagarcanada in reply to AussieNeil]

I want to thank AussieNeil once more for opening my eyes with your concern. Without a doubt, I'll ask for a CBC check within the following month to observe the pattern and determine how best to proceed. I'll go up to her and seek to begin treatment if the disease persists. I believe it would be best if you could provide me with further advice. Actually, a genetic test will determine the two pathways that Dr. Chen has likely proposed. Zanubrutinib alone and in combination could be one therapeutic approach. Venetoclax (oral dose) and Oh-binutuzumab (injection).

[Pierre11]

Hi Sagarcanada,

I think everyone's journey is slightly different. In Jan 2024 my DAT flipped from negative to positive and my haematologist said I would need to start treatment soon...so I started on 2 monthly bloods. Then in Nov my WBC near doubled to 155 from the Sept test, but haemoglobin was still above 100 (110 from 124), and RBC ~3.6 from about 4 prior. These changes were well outside of the normal variability and the slow trend experienced since 2014! Bloods were retested to confirm, and had my genetic markers tested; almost at the same time all my major lymph nodes started growing significantly becoming quite visible, and certainly creating discomfort. 2 weeks later I started targeted chemo (ibrutinib 3mths then with venetoclax next 12 mths).

I have responded extremely well to ibrutinib (nodes down in ~7 days!! WCC to <10 in 2 months, haemoglobin rising and neutrophils also going after an initial decline to<2). DAT back to negative. Only in ramp up phase of Ven.

I do not quite understand my genetic report but it seems I have about 94% mutated IGHV and gain 12q, del 17q.

My haematologist said he has patients with WBC >1000 whom he is not yet recommending for treatment; he looks for the rapid changes as well as physically checking nodes/ spleen/liver.

But having more frequent blood tests might be a good idea.

Cheers

P

[Sagarcanada in reply to Pierre11]

Thank you Pierre11 for your information. I just noticed a shift from DAT-negative to DAT-positive in CLL journey. So far, I understood that the Mutated IGHV is a good prognosis, the Intermediate-risk marker in CLL. How long have you been on the CLL journey so far? When you start treatment. I wish you good luck with this journey.

[Vlaminck in reply to Pierre11]

Thanks for your information but may I ask, what is DAT? Thanks.

[Pierre11 in reply to Vlaminck]

Hi Vlaminck..DAT = Direct Antiglobulin Test. Cheers Peter.

[Vlaminck in reply to Pierre11]

Merci, Pierre!

[New-bee-cell]

Hi Sagar,

I tend to agree with Neil re: the “optimal window”. As my hematologist said, “Ideally, I would treat just before needed, but I’d rather be 6 month early, than 6 months late when you are so symptomatic that you are going into treatment already feeling unwell or having to treat symptoms before we can treat the cancer.”

[OldProf24]

for me the red count dropped low enough I needed a blood transfusion. Treatment started immediately after that.

[Imua]

Thanks to all the contributors for their input , very helpful. On a positive note, you are lucky to be at the Princess Margaret with Dr. Chen who I believe is a CLL specialist. I live in Oakville (about 30 km away from Toronto) and am not apparently in the geographical area to see Dr. Chen.

[rcusher in reply to Imua]

Dr. Chen is one of the top CLL specialist in Canada, I am currently on the Bruin 321 trial which she is heading and currently on Pirtobrutinib for 15 months now. I cannot say enough good things about my treatment at Princess Margaret hospital. BTW, I am 78 and now have all the worst prognostic markers since the start of my CLL journey in 2011. See Bio if interested.

I see you live in Oakville which might be close enough to McMaster hospital who has another top CLL specialist in Dr. Grahame Fraser you might want to check out.

[Sagarcanada in reply to rcusher]

I appreciate the information you provided, RCUsher. We have high hopes for Dr. Chen's ability because I discovered that she is one of Canada's leading specialists in CLL. Your participation in the Bruin 321 experiment definitely would be nice, Could you please tell me when you began treatment? I'd love to hear about your experiences.

[rcusher in reply to Sagarcanada]

If you check my Bio it tells my journey from the beginning till now.

[Sagarcanada in reply to Imua]

I appreciate your insightful comments, Imua. I looked for information on CLL specialists in Canada after my wife was diagnosed with the CLL because I was upset what to do. I found that Dr. Chen in Princes Margaret is a CLL specialist. Prior to that, we would visit the hematologist at Credit Valley Hospital. I sent her an email to request an appointment, and we discovered that she was quite helpful and accommodating. We live a little further away in Brampton, but it's still acceptable to have such a reputable doctor.