When it comes to cancer immunotherapy, there are lots of discoveries. In some cases, some significantly impact the potential for treatment success. In the past, we have seen where antibiotics can have tremendous negative consequences on immunotherapy success. We have learned better the timing of this (within the first month of starting therapy) and ways that seem to help overcome it (using akkermansia and clostridium butyricum). However, with this new data on acetaminophen, I must sound the alarm bells as this is a disastrous problem. We typically do not recommend that our patients take acetaminophen due to liver toxicity. It also does not positively affect the immune response such as ibuprofen or aspirin. However, this advice is often ignored by the patient and is a critical mistake. If you are a cancer patient on immunotherapy, you must avoid acetaminophen-like the plaque. This is vital information, and please share it with all you know. Now let’s get to the science.
Bessede, et al. published in the “Annals of Oncology” that I read in a pre-proof journal; see reference below. The title is “Impact of acetaminophen on the efficacy of immunotherapy in cancer patients.” As this great group of scientists did, they reviewed human data and further confirmed with mouse studies. The overall take-home message is that acetaminophen increases regulatory immune cells, which help protect cancer from your attacking side of the immune system. As you may recall from my book, the immune system has two sides, one that attacks cancer and one that protects it.
In cancer treatment, you want to increase the first and decrease the latter, tipping the balance in favor of cancer attacking. This study showed that acetaminophen given over 24 hours increased Treg and IL-10, both immune suppressive. They also cite previous data that acetaminophen impacts the effects of vaccines, so much so that the WHO recommended not using it close to vaccines. In addition, they saw an increase in immune-suppressive myeloid and plasmacytoid dendritic cells that were immune suppressive. A discussion of dendritic cells always brings up dendritic cell vaccines, but remember that not all dendritic cells want to attack cancer; some are protecting it. This is one factor that has led to their lack of success in cancer treatment. In addition to increasing regulatory cells, acetaminophen also increases the expression of other inhibitory checkpoints such as LAG3 and TIM3. It is essential to mention that Opdualag, approved in March, contains a LAG3 inhibitor and was one of the first new types of immunotherapy supported since 2014.
This study with acetaminophen looks at patients with renal cell carcinoma who were on Opdivo (nivolumab). A horrifying statistic was patients with significant detectable levels of acetaminophen or related metabolites; overall survival was reduced by more than 50% (7.87 vs. 16.56 months). One important thing to remember is that acetaminophen is added to many pain medications often used by patients with cancer. So, it is not only taking acetaminophen itself, such as Tylenol but also what may be in pain medications, such as Lortab or Norco, to name a few. More data is needed, but unless there is no other option, it seems that acetaminophen should be avoided in cancer patients receiving immunotherapy. As with any potential cancer treatments, discuss this with your doctor, and please share this article and the reference below. It is essential to their other patients as well. A good doctor is always happy to learn from their patients.
Jason R. Williams, MD, DABR
Chief of Interventional Oncology/Immunotherapy
Williams Cancer Institute
Author of “The Immunotherapy Revolution, The Best New Hope For Saving Cancer Patients’ Lives”
Reference: Bessede A, Marabelle A, Guégan J, Danlos F, Cousin S, Peyraud F, Chaput N, Spalato M, Roubaud G, Cabart M, Khettab M, Chaibi A, Rey C, Nafia I, Mahon F, Soria J, Italiano A, Impact of acetaminophen on the efficacy of immunotherapy in cancer patients., Annals of Oncology (2022), doi: https://doi.org/10.1016/j.