Thursday, August 28, 2014

Rituxan Maintenance for Follicular Lymphoma

The newest issue of the Journal of Clinical Oncology has a report from the RESORT trial (the name stands for Rituximab Extended Schedule or Re-Treatment. Basically, the trial wanted to see which was more effective: Rituxan Maintenance (their "Extended Schedule") or just waiting until treatment is needed again, and then giving more Rituxan ("Re-Treatment").

In a nutshell, they believe that Re-Treatment when needed is the choice over Rituxan Maintenance for Follicular Lymphoma patients with low tumor burden.

Let me repeat the important part of that: with low tumor burden. The trial focused on patients with this characteristic, and the article is clear about what this means. Basically, low tumor burden has to do with size (less than 7 cm), location (not pressing on any organs), and grade (no B symptoms). What they say about Rituxan Maintenance doesn't apply to patients with more aggressive forms of Follicular Lymphoma. That's important to remember.

It's also important to remember that the RESORT trial is focused on patients whose initial treatment was straight Rituxan. It doesn't necessarily tell us anything about patients who had Rituxan Maintenance after chemo.

So this is fairly limited bunch of folks we're dealing with here.

As for the specifics of the trial: 289 FL patients were given four doses of Rituxan as a first treatment. They were then split randomly into two groups. The first group received Rituxan Maintenance -- one dose every three months. The other group was only given Rituxan when it was necessary, that is, when their lymphoma progressed enough to need it. For both groups, this went on until the Rituxan stopped working ("treatment failure").

For the patients receiving Maintenance, the median time to treatment failure was 4.3 years. For those in the Re-Treatment group, it was 3.9 years. Statistically, there really isn't any difference between them. But over that time, the Maintenance group received a median of 18 doses of Rituxan, while the Re-Treatment group received just 4.

That seems to be the kicker for the researchers -- a few extra months before treatment failure requires an additional 14 doses of Rituxan. And with those doses comes the costs in time and money and whatever emotional costs come with going for treatment. So their conclusion is: for Follicular Lymphoma patients with low tumor burden who received Rituxan as an initial treatment, Rituxan Maintenance really isn't worth it.

Interestingly, the researchers point out that they would love to see a similar trial involving patients whose initial treatment was chemo + Rituxan, comparing those who get Maintenance with those who are Re-Treated with Rituxan as needed. Maintenance is a common practice, but maybe there's reason to ask whether or not there's a better way?

The JCO article was accompanied by an editorial called "End of Rituxan Maintenance for Low Tumor Burden Follicular Lymphoma." It's a title that pretty much sums up the author's position -- he thinks the RESORT trial results tell us everything we need to know. The author doesn't only refer to the RESORT article, but also to an article from March in The Lancet that showed that Rituxan Maintenance in a similar group of patients (low tumor burden Follicular Lymphoma) resulted in a better chance of holding off the lymphoma from returning, compared to those who watched and waited. HOWEVER, the Overall Survival of the two groups was virtually the same, and there was no difference between the two groups in terms of transformation. So while the article from The Lancet might seem like a win for Rituxan Maintenance (and that's certainly the way I wrote about it, as you can see from the link), looking at different outcomes might paint a different picture of that data.

(And, to be fair, The Lancet article and the RESORT article compared two different groups. One said Maintenance was better than watching and waiting, while the other said it was not as good as treating as needed.)

My conclusion?

As with many things related to Follicular Lymphoma, we still have no real, solid evidence that one strategy is definitely better than another. Despite the confidence of that title, I don't think we've seen the "End of Rituxan Maintenance" for FL patients with low tumor burden. It might provide a push for a patient or oncologist who is sitting on the fence, but I'm sure there are plenty of folks who will continue the practice. The RESORT results didn't say Maintenance was bad or harmful, only that there might be a better way.

I can remember talking to Dr. R about Maintenance after my six rounds of Rituxan. He talked me out of it, saying there was better evidence that Maintenance worked after chemo than after straight Rituxan, and that his philosophy was to treat when necessary (very much in line with the Re-Treatment approach from RESORT). Dr. R certainly seems wise, four and a half years later, when I still haven't needed Re-Treatment of any kind.

Of course, one patient does not make a trial, so my isolated experience doesn't mean much. The lesson, instead, from my experience is that an open, two-way conversation with your oncologust is necessary when it comes time for treatment.

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