Acetaminophen and Immunotherapy

[210savannah]

Has anyone else heard of this? Does is have any bearing on CLL patients on BTK inhibitors?

facebook.com/25998443394/po...

[AussieNeil Partner Administrator]

Per the referenced Medpag Today article:-

Acetaminophen Blunts Antitumor Activity of Immunotherapy

— Lower response rates, worse survival seen in patients with detectable levels of the antipyretic

(Acetaminophen will be better known as Tylenol/Panadol/APAP/Paracetamol - Neil)

medpagetoday.com/hematology...

'Patients starting cancer immunotherapy with detectable levels of acetaminophen had worse outcomes, including response rate, progression-free survival (PFS), and overall survival (OS), in data from three patient cohorts.

In the largest of the three studies (N=392), patients with detectable acetaminophen had a 33% lower likelihood of survival as compared with patients who did not have detectable acetaminophen at the start of treatment with nivolumab (Opdivo).

An analysis of 297 patients treated with a PD-1/L1 inhibitor (alone or in combination with a CTLA-4 inhibitor) showed about a 50% reduction in PFS and OS among patients with detectable acetaminophen.

:

Together, the findings suggested that acetaminophen decreases T cell-mediated antitumor immunity in advanced cancer, the authors said. "It is unlikely that our data are the result of bias or unmeasured confounding."' (My emphasis)

So these studies showed a lower likelihood of survival when there was detectable acetaminophen when being treated with a checkpoint inhibitor Nivolumab. Per en.wikipedia.org/wiki/Nivol...

Nivolumab "is a type of immunotherapy and works as a checkpoint inhibitor, blocking a signal that prevents activation of T cells from attacking the cancer."

Nivolumab is not used for the treatment of CLL. Checkpoint inhibitors don't work very well for CLL treatments, because CLL tends to drive T cell to exhaustion. Also, with the exception CAR-T therapy, CLL treatments don't rely on T cell assistance to kill CLL cells, so I don't see relevance to our community other than possibly CAR-T treatment.

On a personal note, not long after I began treatment which began with a BTKi inhibitor (acalabrutinib), I ended up with febrile neutropenia and ended up taking the maximum dose of acetaminophen for at least a couple of months. I'm still here.

Neil

[Walkingtall62 in reply to AussieNeil]

Hope I read this right. Does this mean taking paracetamol every day is not good for me - apart from being good for my head. It has caffeine in too!

[AussieNeil Partner Administrator in reply to Walkingtall62]

Not at all! With the possible exception of CAR-T or if you are in the clinical trial lankisterguy found, then there is no reason for you to be concerned about taking paracetamol when you have CLL. As Len pointed out, the findings of this research needs to be taken into account with the research into improving the immune system, looking into the beneficial effects of BTKi drugs and T cells, but not many of us are involved in that research.

Neil

[Walkingtall62 in reply to AussieNeil]

Thanks Neil. My brain isn’t functioning too well. Even the air outside is frozen🙆‍♀️. Phew, I need my dose of paracetamol and caffeine, no idea why, but heh! Take care

[lankisterguy Volunteer]

Hi 210savannah,

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From reading the links you provided (thanks for including them) the 3 studies seemed focused on an interaction between acetaminophen and Opdivo / nivolumab, which is usually used for solid tumor cancers.

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However there is a current Phase 1 clinical trial at MD Anderson that uses that drug in combinations to treat CLL- clinicaltrials.gov/ct2/show...

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So we may need to watch for other studies and trials to see if there is any reason to be concerned whether acetaminophen could cause problems with our T-cells, which the experts believe are already "exhausted" by some aspect of CLL in our bodies.

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There are also some current investigations trying to understand possible beneficial interactions between BTK inhibitors and T-cells. So those studies might need to exclude the use of acetaminophen or account for it in those trials.

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Thanks for posting this question / concern.

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Len

[CycleWonder in reply to lankisterguy]

This is somewhat disheartening. We are not supposed to take any NSAID since these drugs interfere with platelet production. I have been relying on Tylenol for headaches and other aches and pains. I am loathe to give up the one pain reliever left for us!

[210savannah in reply to CycleWonder]

According to what others have stated, it does not imply CLL patients and/or BTK inhibitors. I am like you - Acetaminophen is my “go to”.