Imbruvica and UTI

[Agatesup]

I am a male and have been on Imbruvica for 2 years. Have had 3 bouts with UTI over last 5 months. Anyone else on Imbruvica experience UTI? I am always healthy and clean.

[lankisterguy Volunteer]

Hi Agatesup,

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If you follow this link, you can find 50 previous discussions about UTI's -

healthunlocked.com/cllsuppo...

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I would expect that frequent UTIs are a common side effect of CLL, and likely not necessarily a side effect of Imbruvica.

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While treatment can reduce most of the symptoms of CLL, the medical researchers have not yet found a way to fix the damage that CLL does to our immune systems. Some of the research is focused on "exhausted" T-cells that allow infections and 2nd cancers to be more common among CLL patients, whether treated or untreated. Skin cancer is 5-8 times more active, even more than with other Lymphomas.

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Len

[Ngtinfu in reply to lankisterguy]

Len, something you said in your post caught my eye as I have been wondering about our immune systems. If CLL damages our immune systems is delaying treatment (W&W) causing more harm? Would it not make sense to treat before our immune systems are damaged? A secondary question would be: if one is treated to the point of not having any residual disease, can one then be vaccinated with "live" vaccinations?

[AussieNeil Partner Administrator in reply to Ngtinfu]

From my perspective, CLL inhibits our immune system in a number of ways while we are on watch and wait - it's not necessarily permanent damage, but it can take a while for recovery. Off the top of my head, CLL inhibits our immune system by:

1) Reducing bone marrow capacity through overcrowding, thereby lowering our production of other infection fighting white blood cells

2) Inhibiting T cell function and reversing the T4:T8 ratio

3) Inhibiting of plasma cell production of immunoglobulins

Remove the CLL cells and these impacts are reversible, though you also need to reduce the impact of the treatment on healthy B-cells to address (3).

The problem is that current CLL treatments also inhibit bone marrow production, which is why neutropenia, anaemia, thrombocytopenia, etc, can be much worse during treatment than during watch and wait - hence W&W. The good news is that we are approaching the point with current treatments where specialists consider that it may be better to treat earlier and trials are underway with some patients treated earlier than per current guideline recommendations.

With respect to your very good question about whether it might be possible to give patients who have achieved U-MRD live vaccinations, that would depend on how well their immune systems have recovered post treatment (or how much it is being suppressed if on a maintenance treatment).

Neil

[Ngtinfu in reply to AussieNeil]

Neil, thank you very much for your thoughtful reply. It gives me hope that maybe, we all can have completely normal lives at some point when there is greater understanding of how all of this plays out.

[lankisterguy Volunteer in reply to AussieNeil]

I believe that Dr. Furman would be far less optimistic than Neil's comments above.

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I have been U-MRD for over 3 years, but my chronic viral infection with HHV-6 and my skin problems with excessive T-cells in my epidermis causing psoriasis have not reduced in measurable ways. My IGA & IGM are well below minimum, (my IGG remains at the low end of normal- ever since diagnosis).

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I have asked Dr. F several times why I don't see my immune system recovering despite no measurable CLL cells out of 10,000 white cells checked, he says "we just don't know."

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When I spoke at Abbvie's HQ to an audience of 400, they asked me what I wanted next beyond Venetoclax, and I replied "find a way to fix my immune system, please".

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Len

[lankisterguy Volunteer in reply to AussieNeil]

Here is more info from the CLL Society Newsletter this week

cllsociety.org/2019/09/ash-...

ASH 2018: Dr. Neil Kay on Bone Marrow Dysfunction in Chronic Lymphocytic Leukemia (CLL)

At ASH 2018, I sat down with Dr. Neil Kay out of the Mayo Clinic, Rochester, MN to talk about the basic science research being done by the lab at Mayo where he collaborates with a lab team including Kay Medina, Ph. D. concerning how CLL impacts the bone marrow and ultimately our immunity.

The bone marrow is where all the action is. The marrow gives birth to the blood cells that give us life. It is also where our cancerous CLL cells hang out, grow, and cause their malignant effects.

That is why studying the bone marrow is so critical in understanding CLL.

Takeaways:

Even before CLL is treated with medications that might damage the bone marrow, the CLL itself has had a negative impact of the hematopoietic stem cells that live there and make our cells.

This is not simply a case of the healthy cells being crowded out by uncontrolled growth of the cancerous chronic lymphocytic leukemia cells in the marrow. That only happens with much more advanced disease.

What seems to be happening is that “healthy normal” bone marrow stem cells themselves are less vigorous in producing all the cells that live in the blood, nodes and spleen.

In other words, the bone marrow doesn’t work normally even in early stage CLL, potentially leading to low red blood cells, white blood cells (our immune system), and platelets.

Tumor necrosis factor (TNF-α), an inflammatory cytokine (enzyme), may play a role in this bone marrow suppression.

We have existing drugs that block TNF being used to treat inflammatory arthritis such as Rheumatoid Arthritis and other inflammatory diseases. Patients on these medications who also have CLL could be very interesting to study.

Helping the bone marrow function to recover, theoretically could lead to improved immunity and ultimately lower our risk for serious infections and second cancers.

Conclusions:

Basic science research is so important in CLL.

If you have CLL and are also on medication such as adalimumab (Humira) or something similar for an inflammatory condition, please consider reaching out to us at [e-mail] and we can connect you with Drs. Kay and Medinas’ lab team to see if you would be a fit for their research.

This area of research is increasingly relevant as fewer and fewer of us are dying of CLL while more and more are dying of second cancers and infections. We need to reboot our immunity.

At the CLL Society, we have identified 4 top priorities for future CLL research and reconstituting the immune system is one of them.

Here is my ASH 2018 interview with Dr. Neil Kay on bone marrow dysfunction in CLL:

cllsociety.org/2019/09/ash-...

Here is the link to the ASH abstract: Bone Marrow Hematopoietic Dysfunction in Untreated Chronic Lymphocytic Leukemia Is Partially Mediated By Exposure to Constituents of the Leukemic Microenvironment.

Enjoy.

Thanks

Brian

Brian Koffman MDCM (retired) MS Ed

Co-Founder, Executive VP and Chief Medical Officer

CLL Society, Inc.

[lankisterguy Volunteer in reply to Ngtinfu]

Hi Nhtinfu

The answer and our immune systems are incredibly complex. So as I said originally the medical researchers have not yet found a way to fix the damage that CLL does to our immune systems Even how and what has been damaged is not well understood.

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So here is one of our pinned posts that answers your question about early treatment:

healthunlocked.com/cllsuppo...

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Len

[Ngtinfu in reply to lankisterguy]

Len, thank you for your reply. I'm not sure when these studies took place, but it seems like they were addressing actual chemotherapy. But with the new agents, I don't see how earlier treatment could be harmful - other than starting the clock a bit earlier should these novel agents prove to have a limited time of efficacy. I guess time will tell.

[AussieNeil Partner Administrator in reply to Ngtinfu]

Time for a re-read. The opening video from Dr Lamanna was recorded less than a a year ago and the title of the post is "When will I need treatment? Is Watch and Wait still the best option with newer treatments", i.e. non-chemo treatments Len's post covers how non-chemo treatments are resulting in changes to treatment paradigms as reflected in CLL management guideline updates. It's well worth taking the time to review the referenced presentations given your concerns.

[Ngtinfu in reply to AussieNeil]

Thanks!

[BeckyLUSA]

I presume you went to the doctor and confirmed the infection with dips etc. Make sure you are drinking plenty of water. Insufficient water intake can exacerbate a UTI.

For me personally, the Ibrutinib will give me a phantom UTI if I do not drink enough. I will get all of the symptoms of a UTI, but tests come back negative. It takes about 6-8 of diligent water drinking to get the symptoms to stop, I have not had any true UTI’s while on the Ibrutinib.

Good luck!

BeckyL USA

[Ellieoak in reply to BeckyLUSA]

Becky, you are so right. When I was taking Imbruvica I had to really watch how much water I took in. When I slowed down, the UTIs would show up out of know where. Drink, drink, drink. Anna

[colincll10]

what is uti

[AussieNeil Partner Administrator in reply to colincll10]

Urinary Tract Infection: en.m.wikipedia.org/wiki/Uri...

[annacd]

I have been on 7 rounds of antibiotics for UTI since June. I just keep getting them one after another. My imbruvica has been reduced to 280. I see a urologist on Monday.