PV patients and Common Variable Immune Deficiency Adult Onset

[Psteuer]

I have been a PV patient since 2012 and on Ruxolitinib 20mg 2xday since 2017. In the past two years my IG's have begun to fall as have my B cells and T cells. My oncologist referred me to Immunology. After several subset blood tests, they have determined that my immune system is failing and I have been diagnosed with CVID.

I have asked this question in other online MPN forums. Have any PV patients in this forum experienced a similar phenomenon with IG's (Immunoglobulins), B and T cells depleting while on Ruxolitinib?

Playing medical sleuth here because doctors keep asking me if Ruxolitinib may be causing this depletion. I have spoken with Incyte Pharma and they claim nothing like this has been reported about the drug. I have done exhausting searches of hematology abstracts and have only found one that mentions this.

Thanks for your help. Patricia

[EPguy]

There are some reports on this

"inflammatory cytokines, including TNF-alpha, IL-5, IL-6, and IL-1B, were found to be significantly downregulated in T cells isolated from the (Rux) patients" This should be a good thing and is a key reason to take Rux, but:

"treatment with ruxolitinib resulted in a long-lasting reduction in circulating Tregs (Regulatory T cells). Dose reduction or withdrawal of the drug failed to restore the Treg subset to values comparable to those of the control, suggesting that the effect of ruxolitinib was irreversible. The authors suggested that the severe reduction in circulating Tregs observed in their patients exposed to ruxolitinib may constitute a major cause of immunosurveillance disruption"

This report has further links on the subject.

frontiersin.org/articles/10...

Rux is well known to inhibit immune function, maybe these are some of the ways that happens. But this is the 1st I've seen that suggests permanent reductions, if valid this is a concern. There must be other studies with more info on this.

[Psteuer in reply to EPguy]

Thank you very much for the abstract and your response. It seems that Ruxolitinib may indeed be tanking my immune system. I will speak with my specialist about this on 9/12. Thank you for the reference. Much appreciated.

[EPguy in reply to Psteuer]

I think most MPN patients do not get T-cells measured. I know from covid research it is not easy to do. Is there a certain reason your Dr ordered it? Maybe it's a good test for any one on Rux.

[Psteuer in reply to EPguy]

I have two oncologists, one at UCLA in Los Angeles - my local specialist who monitors my PV every three months and refills my Ruxolitinib prescriptions. He knows little about MPN's but was recommended by the Hem/Onc MPN specialist who is my go to person about all things MPN at Stanford in Palo Alto, CA. I do telemedicine visits with him twice a year to remain his patient. He has been my MPN Specialist since 2016. We moved to LA two years ago. About a year after we moved, I began to experience more than the usual amount of fatigue that PV and other MPN's can report. I mentioned it to my local doctor and he ordered my Immunoglobulins checked. Some of them were low. He referred me to UCLA Immunology and cautioned me not to accept any confirmation bias on their part about my experience being caused by PV. Immunology ordered MANY additional subset tests on IG's, CD4, CD8, T and B cells. They concluded a year ago that I was evolving into Common Variable Immune Deficiency, but my T cells had not yet dropped low enough to meet the diagnostic criteria required. That changed in August of this year. As a result of this experience, I would recommend that all patients on Ruxolitinib advocate for themselves to have referrals to competent Immunologists if they begin to experience more than the typical fatigue MPN's can cause. Since the damage to my immune system is likely permanent and irreversible, I doubt my Stanford specialist will recommend changing to a different therapy. In addition to the immune system deregulation, Ruxolitinib patients with CVID are far more at risk for lymphomas, gastric, colorectal and breast cancer. I will be asking my specialist about how to get properly screened for early detection about lymphomas or gastric cancers. I already do the proper preventative tests for colorectal and breast cancers.

[EPguy in reply to Psteuer]

Quite a history. I understand your journey a bit better. Your experience is quite valuable, and with the report we unearthed here I would like to make a fresh post on the importance of monitoring T-cells on Rux (or maybe any Jak-i) This seems like it should/could be an FDA Black Box Warning.

[Wildwood6]

Hi Patricia. Sorry to hear about your diagnosis. I was diagnosed with MF earlier this year and am now on watch and wait, but I was diagnosed with hypogammaglobuliminea (low IgG) in 2013 and briefly diagnosed with CVID last year (ie my diagnoses were the other way round). I hover on the edge between the 2 diagnoses. I know my immunology team well and quizzed them intensely about any connection between my MPN and immunoglobulin deficiency and was told that none was known. My immunologists are based at the Royal Free Hospital Hampstead London, one of the UK’s leading immunology centres. However, both the immunologists and the haematologists have told me that it is known that Ruxolitinub is not for me, because it would adversely affect my immune system. Good luck. Myke

[EPguy in reply to Wildwood6]

We seem to have some extra clarity on your team's suggestion. T-cells in particular may be a marker for this problem.

[Psteuer in reply to Wildwood6]

Myke - thanks for your message. I'm sorry to hear about the MF and watch and wait. Always a risk for those of us with PV. I may have had CVID and low IG's for awhile - perhaps even before I was diagnosed with PV in 2012, but I didn't complain about EXTRA fatigue until last year which is when the low IG's and CVID were discovered. By then I had been taking Ruxolitinib for 5 years. I will have to ask my Stanford Oncologist whether or not he believes I should continue Ruxolitinib or move to another therapeutic medication to slow the activity in my marrow. I wish you good luck and good health. Patricia

[jon1972 in reply to Psteuer]

I would be very curious as to whether Interferon would be recommended in your situation or if that would be contraindicated.

[mhos61 in reply to Psteuer]

I don’t know if this is helpful or not. There is a forum member ’katiewalsh’ who has CVID. I don’t think she’s on ruxolitinib though.