ASH: Rituxan vs. Watching and Waiting

Another interesting abstract from ASH: "Frontline Rituximab Monotherapy Induction Versus a Watch and Wait Approach For Asymptomatic Advanced Stage Follicular Lymphoma: A Cost-Effectiveness Analysis," from several Canadian researchers. The whole "do I treat or do I wait?" debate has been going on for a while, and we don't have a definitive answer. This paper provides another perspective (though, not, I would argue, a definitive answer.)


I am, of course, a watch-and-waiter, so my bias tends to be toward this approach, if it makes sense medically and emotionally for the patient. The argument I received for watching and waiting is essentially the same that most patients hear: starting treatment right away has not been shown to increase overall survival. If there are a limited number of treatments available to Follicular Lymphoma patients, it makes sense to hold off for as long as possible before starting to chip away at that list. Also, if watching and waiting works, there's no sense in starting a treatment that could potentially result in side effects, even if they are minimal ("Do no harm," as Dr. R puts it -- choose the treatment that will give the most benefit with the least damage.)

The authors of this paper take a different look at this controversy, focusing on cost. Now, watch and wait also has that cost advantage: no treatment = no outlay. But they look at this from a different angle.

They note that the studies that have looked at watching and waiting vs. treatment all looked at some form of chemotherapy as the treatment being compared. None looked at Rituxan as an immediate first treatment. They found that a study from 2010 showed that while there was no overall survival benefit to Rituxan instead of W & W, there was a benefit in Time to Initiation of Next Treatment. In other words, Watch and Waiters needed to be treated sooner than those who took Rituxan.

The researchers developed a hypothetical model, using data from published studies. Essentially, they created fake 60 year old patients (yes, I know "fake" is a loaded term, but I also know that not all Folliuclar Lymphoma patients are 60 years old) and ran a model of what was likely to happen to them over the course of several years. They looked at the patient in 6 month intervals: based on published data about FL patients, and various median times to treatment, what is likely to happen 6 months after diagnosis? Would they need treatment? And after 6 more months, what would happen? And six months after that?

Based on this hypothetical model, they determined when these patients would likely need a first treatment, a second treatment, Rituxan Maintenance, salvage treatment, palliative care, etc -- basically running through their entire post-diagnosis lives. They ran the model with patients who began by watching and waiting, and who began by getting Rituxan right away. All of the patients received Bendamutine + Rituxan, then Rituxan Maintenance, with a maximum of 3 different treatments. Overall, they ran the model on 10,000 patients. They focused on how much all of that care would cost, based on actual Canadian health care system figures.

The results showed very little difference in Overall Survival, as was the case with other studies (and considering the data was based on actual studies, it is to be expected). So there is no arguing that one is better than the other in terms of effectiveness.

However, because the Rituxan patients required more time until treatment, the overall average monetary cost was lower for them: $59,061 for the Rituxan patients, and $74,531 for the Watch and Waiters. They argue that there is a lot of money being spent for no real benefit.

This is certainly one more variable to consider in choosing between the two strategies. While it is a simulation, it's based on data from actual patients, which does lend it some credibility. And I'm certainly in favor of reducing costs, as long as care is not comprimised.

It will be interesting to see what the reaction is for this one. I don't think treatment strategies would change based just on cost alone (that doesn't seem to be an issue right now, anyway), though it could be one more factor that tips the scales for some individual doctors in making a recommendation to patients. I think any effects from this are going to be pretty subtle.