Would Imbruvica lower immunity levels? For how long?

[AshGS]

As I heard that one important side effect is that we are prone to serious infections

[Jacksc06]

Hi. I found this hope it is helpful. "Ibrutinib can decrease the number of different types of cells in your blood. These effects are usually mild but can result in an increased risk of bleeding and developing infections. Ibrutinib can also cause a temporary increase in the number of lymphocytes (a type of white blood cell) in your blood". Perhaps some of the more learned on this forum could advise you in more detail. Best wishes.

[mantana]

I'm not a specialist, just trying to rationalize here. Please correct me if I'm wrong.

My understanding is immunity might improve for patients with severe CLL. On the other hand, immunity will likely get worse for patients with not-so-severe CLL, or healthy patients.

The rationale behind my thinking is that Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor.

BTK plays a crucial role in B cell development:

en.wikipedia.org/wiki/Bruto...

Because Ibrutinib inhibits BTK, it will affect development of cancerous B cells, but also of healthy B cells.

Please note that Ibrutinib will not stop the development of all B cells. Some cancerous B cells will still develop; some healthy B cells will also still develop.

1) My rationalization why Ibrutinib might improve immunity for patients with severe CLL:

- patients with severe CLL have cancerous B cells crowding out other cells in bone marrow, where blood cells are produced; they will also affect spleen and lymph nodes in a similar way

- once Ibrutinib starts to work, cancerous cells will be flushed from bone marrow, spleen

and lymph nodes - thanks to this, your body will finally be able to produce more-or-less the right amounts of healthy lymphocytes - B cells (partially "killed" by Ibrutinib), T cells, Natural Killer cells, and also other types of infection fighting blood cells, like Neutrophils

2) My rationalization why Ibrutinib might decrease immunity for patients with not-so-severe CLL (i.e. extra cancerous CLL cells in blood, bone marrow and spleen, but also plenty of healthy cells):

- the main problem I see with BTK inhibitors like Ibrutinib or Acalabrutinib is that they not only target cancerous B cells, but also healthy B cells. That's why anyone on BTK inhibitors will not be as immune as a healthy person.

[AussieNeil Administrator]

Hi Ash,

First, remember that you are immune compromised from the moment you have CLL. All CLL treatments lower immunity initially, but the immunity reduction from the CLL reduces as the CLL cells are killed off. All CLL treatments to some degree can cause neutropenia - a low neutrophil count. This puts you at increased risk of bacterial and fungal infections. That's one reason why you have regular blood tests during treatment. You were hopefully given some information on how to be careful to reduce your infection risk during treatment, including what foods to avoid. Any neutropenia generally improves as the CLL infiltration of the bone marrow is reduced.

Finally, all CLL treatments kill off healthy B-cells (lymphocytes) and perhaps T- cells, as well as the cancerous CLL cells. The resulting low lymphocyte count puts you at higher risk of viral infections. (This is why it us common to prescribe an antiviral during treatment). The low lymphocyte count may also lower your antibody counts (IgA, IgG and IgM). However, IgA and IgM have been observed to improve after long term Ibrutinib use.

Neil

[larrymarion in reply to AussieNeil]

My IgA and IgM bounced up a bit after several years on Ibrutinib, but then they plateaued at about a third or less the lower range of "normal" levels. My understanding is that as the bone marrow recovers a bit from the CLL it manages to manufacture a modest number of healthy B and T cells.

[Berrytog]

I am informed when reading Andrew Schorr's CLL site during his interviews with American CLL specialists, particularly from MD Andeson that those taking Ibrutinib fro some time stand a better than average chance with Covid 19

[AdrianUK in reply to Berrytog]

I think we should be very cautious about the idea that ibrutinib protects against COVID19. Especially in the early stages. A recent randomised controlled trial has shown that Dexamethasone saves lives of people who are presenting with COVID19 pneumonia but does NOT help earlier in the disease and by suppressing the immune system may even be harmful. IF Ibrutinib does help severely ill patients with COVID19, which is being trialed at the moment and may or may not not work, it really does not follow that ibrutnib would also help early in the disease. So we should instead follow the precautionary principle that EVERYONE with CLL has poor lymphocyte fuynction as Neil explained and therefore are at risk of not being able to produce antibodies. If you click on my name you can find some recent data about this in a post I wrote a couple of days ago which in turn links to a much longer post with no fewer than four case series of symptomatic COVID19 in blood cancer patients.