A blog reader (thanks!!!) sent me a couple of links that started me off on a unexpectedly startling and, in the end, rather confusing search mission. Who’d have thought that aspirin, = acetylsalicylic acid, might possibly be a bad thing for myeloma patients to take? (Please note my use of the conditional tense.) I concluded that it would probably be a good idea to write a post on this topic for two main reasons: 1. aspirin is currently being tested in more than a couple of myeloma clinical trials (check www.clinicaltrials.gov) and 2. there are more than 50 aspirin-myeloma studies in PubMed…

What does aspirin have to do with myeloma? The answer may be obvious to some, but it wasn’t to me…not immediately, anyway. It is because of aspirin’s blood-thinning properties. It’s because aspirin interferes with our blood’s clotting action, which is good, of course, if we are taking a drug that could cause potentially fatal blood clots, such as thalidomide. And, in fact, if you look at the clinical trials, aspirin is being given to patients on thalidomide or its derivatives. Okay, now we can keep going…

The first link led me to this letter, written by Dr. Kast and published in “Blood” in 2006: http://goo.gl/e1ZVn Here we learn that aspirin and other COX inhibitors have a long documented history of increasing the circulating levels of tumour necrosis factor-alpha…What what whaaaaaat? I didn’t know that. What I did and do know is that TNF-alpha is a major GROWTH FACTOR for myeloma cells…not quite as bad as IL-6, but most definitely one of the really really bad guys… 

Dr. Kast suggests that TNF levels simply be monitored in myeloma patients who take aspirin as part of their therapy. Should their TNF levels increase, he writes, then steps to reverse that elevation or alternative thrombosis prevention measures should be taken. That sounds reasonable…but let’s keep reading…

The second link took me to a 1996 study, published in “Immunology”: http://goo.gl/mrgsV This study examined the effects of aspirin and ibuprofen not just on TNF-alpha but also on other myeloma growth and survival factors such as IL-6 and IL-1 beta. By now I think all myeloma patients must be familiar with IL-6. As for IL-1 beta, well, among other things, it is implicated in the progression from SMM to MM, so those of us with asymptomatic myeloma (SMM) should pay particular attention: http://margaret.healthblogs.org/life-with-myeloma/what-is-multiple-myeloma/myeloma-supplements-and-il-1-beta/).

The “Immunology” study is available for free online and is quite easy to read (just click on “complete article” and wait until it downloads). The gist: a few weeks after a group of healthy volunteers had stopped taking their daily aspirin and ibuprofen doses, their IL-1 beta and TNF levels had increased compared to the pre-experiment period.

Another bad thing that happened is that IL-2, = another pro-inflammatory cytokine, also increased quite a lot. Two observations, though: 1. some sort of different stimuli were used in this study, and I am not entirely sure what that means (I would need more time, more time than I have right now, to check out all this stuff…); 2. the study was published 15 years ago, so it is a bit dated…Still, since I found the data a bit alarming, I decided to do a bit more digging…

I found two other 2006 studies on this topic. I couldn’t find any more recent (than 2006) studies, I mean on the possibly dangerous consequences of using aspirin in conventional myeloma treatments, which I found very odd, but I might have missed a study or two. Anyway, let’s begin with the first, which is, again, available for free online and starts off from Dr. Kast’s above-mentioned letter: http://goo.gl/FgkV8

Let’s look at a couple of key sentences: aspirin, according to these authors, may, in fact, have positive effects on survival in patients with MM. […] Malignant plasma cells often overexpress cyclooxygenase 2 (COX-2) and this overexpression has been found to be a predictor of poor outcomes in MM patients. A few paragraphs later, we read that aspirin inhibits both COX-1 and COX-2 and this may serve as a rationale for possible antineoplastic properties in MM.

The authors then refer to a study they carried out in 2005 (this full study is also available for free (yaaay!): http://goo.gl/ryG3S) on myeloma patients following the DVd-T regimen and divided into three groups. The group that took aspirin apparently had a better response than the group that did not. And so the authors conclude: While these preclinical and clinical observations suggest that low-dose aspirin may have antineoplastic properties in patients with MM, they are not definitive and render the alternate hypothesis (that aspirin has a deleterious effect on the survival of patients with MM) much less likely.

Dr. Kast, author of the above-mentioned “Blood” letter, wrote a response, titled “Aspirin, TNF-alpha, NFkB, and survival in multiple myeloma: the importance of measuring TNF-alpha”: http://goo.gl/RXfoU The abstract tells us that there are conflicting reports on aspirin. On the one hand it has been shown to slightly increase survival duration in multiple myeloma, which obviously is a good thing…on the other, caution is raised about use of aspirin and COX inhibitors generally in inflammatory states and specifically in myeloma. Should they increase tumor necrosis factor-alpha they could exacerbate disease. Exacerbate disease, eh? Well, we certainly do not want that!

At this point, I should announce that, even though I have read the full study, my NEW BLOG POLICY is NOT to quote directly from any copyrighted material. That doesn’t mean that I will stop reading full studies, of course, and reporting on any important bits…I just won’t use direct quotes, that’s all. So I can tell you that Dr. Kast concludes that the use of aspirin in myeloma conventional treatments is okay, provided that TNF levels are monitored, particularly should TNF levels increase together with myeloma progression…

I would also like to mention that, according to Dr. Kast’s review of the scientific literature on this topic, the data is conflicting. Aspirin, and similar COX inhibitors, he writes, can either delay or accelerate myeloma progression…Confused?

Okay, let’s see if we can figure this out.

• First point: TNF-alpha is overexpressed in myeloma, which basically means that it is being produced in larger quantities than needed, and that is a bad thing, since TNF-alpha helps myeloma cells survive, as we have seen.
• Second point: aspirin increases the levels of TNF-alpha. Dr. Kast reminds us that TNF levels go up as myeloma progresses…hence, lowering TNF may delay progression. That makes sense, right?

Well, it’s not that simple. Since 1996, different studies have shown that aspirin decreases, increases or does nothing to TNF levels. No kidding. Frustrating, eh?

So where does all this leave us? Well, just to be on the safe side, I will never take any aspirin again (UPDATE 2017: I have changed my mind on this matter, based on other readings, and I will take, and indeed have taken!, aspirin when needed). More importantly, if I were doing chemotherapy AND taking aspirin to counter any possible clotting problems, I would have my docs monitor my TNF levels frequently and carefully. Or I might ask for a different something-or-other to prevent the clotting…

You never know…