Rituxan vs Watch and Wait (Again)

A couple of months ago, I wrote that I thought it was time to move on from discussing the whole Watch-and-Wait vs Rituxan choice -- whether or not it is best to treat with Rituxan right after diagnosis, or better to wait until treatment is necessary (as I did). There has been so much research done on whether or not Watching and Waiting is the best choice, given how effective Rituxan is, with its relatively mild side effects. Lots of good reasons for choosing one over the other, though there was no evidence that one had a better Overall Survival effect than the other. I said it was time to move on to other things, since we weren't getting anything new.

And now, we have something new.

The journal Cancer has published a study that shows that getting Rituxan is more cost-effective over the life of the Follicular Lymphoma patient than Watching and Waiting. In other words, if you take Rituxan (with or without maintenance) soon after diagnosis, you'll spend less money on treatments if and when the FL comes back than you would if you had just waited until treatment was necessary. The abstract for the study is here, and a commentary on it from Cancer Network can be found here.


Of course, I have some issues with the study and its implications. I hope you weren't thinking this was going to be some kind of Final Answer to this issue.

The researchers conducted a statistical study using something called a Markov Model, which is a fascinating tool that allows for the complexity of a medical situation like having a Follicular Lymphoma patient have to have many treatments over a lifetime. I don't think I can really explain it in very simple terms, but basically, it measures how a patient is likely to do after receiving a treatment, what kind of options will be available when another treatment is necessary, what the likelihood will be of choosing one treatment over another, and moving on down the line. Statistically, of course -- all of the numbers and choices are based on what we already know about Follicular Lymphoma.

Anyway, the results of their modelling show that someone who receives Rituxan soon after diagnosis will likely end up paying $59,953 (Canadian dollars) for treatments over their lifetime. Someone who had Rituxan, plus Rituxan Maintenance would pay $67,489, and someone who watched and waited would pay $75,895. Again, these are based on statistical models: statistics show that someone who watched and waited would likely need another treatment in XX months or years, and that treatment would likely be XXX, and would be followed in XXX months by XXXX treatment. This isn't an actual single patient with exact treatment recommendations.

The study also measures (again, statistically) Quality-Adjusted Life Years (QALY). This is, again, how many years someone would likely live disease-free. It's a little bit complex -- it takes into account the partial years a patient in disease free. So using me as an example, I have lived 7 years and 4 months since my diagnosis. BUT, I have never actually been disease-free in that time, having achieved a Partial Response after Rutuxan, and then having various levels of waxing-and-waning disease since then. On the other hand, I haven't missed any work because of it. By some statistical measure, they can figure out how many of my 7.25 years are Quality-Adjusted Years. I assume it will be less than 7.25.

(That's a lot of statistics from someone who keeps talking about how much he hates statistics.)

The researchers found that Rituxan plus Rituxan Maintenance right after diagnosis gave 6.28 Quality-Adjusted Life Years, with Rituxan-only gave 6.16 and Watching and Waiting gave 5.71. (The difference is a matter of months.)

So either form of Rituxan, by these measures, beats out Watching and Waiting.

Before you start regretting your watch-and-wait decision (and let me clear: I do not), let's look at this a little more closely.

First, let me point out yet again that this is a statistical study. It is uses statistics based on what decisions people have made in the past to determine the outcomes. I think that matters -- a lot. I remember, many years ago, when I saw Dr. C the lymphoma specialist soon after my diagnosis (not Dr. R, my regular ol' oncologist), he told me that anything I read on the internet is already out of date. I thought of that as I read this: this is based on treatment decisions (and costs) that were available at the time of the study. They can't really anticipate that, in 10 years, some super combination of monoclonal antibody, kinase inhibitor, and anti-PD1 treatments will be available, and will help 75% of patients, and cost less than Rituxan costs now. They can guess at that, but they can't really know. They can only know that after Rituxan Maintenance, a patient is likely to try Rituxan, and that will cost X, and then will become Rituxan resistant, and will try straight Bendamustine, and that will cost X, and so on. So like most statistical models, this is based on a bets guess (and admittedly, that is sometimes a frighteningly good guess).

I think it also matters that this study takes place in Canada. It could have been the U.S., or Brazil, or the U.K., or New Zealand. Whatever. It's in one specific place at one specific time. That's going to have a significant impact on the cost of treatments, but also the availability of treatments (as the Lymphoma Coalition's Report Card makes very, very clear). Change the time and location, and those statistics are likely to change. That may actually favor Rituxan, as its trademark protection expires, at least in the U.S. Though it may favor Watching and Waiting, too, in other places where treatments are more costly.

I said it in the last post I wrote about this debate, linked above, and I'll say it again: There is a lot that goes into the initial decision on a treatment after diagnosis. Cost certainly matters. Physical state obviously matters. But so does emotional state. As much as we can learn from past statistics, and as much as it would be great to consider what future treatments might be available, what matters to most of us, at that time, is what is happening RIGHT NOW, at diagnosis.

So I think this study adds some interesting stuff to talk about. But I maintain my power as Lympho Bob to say: this debate still isn't settled. Talk to your doctor about every factor that might play a part in making your treatment decisions.