ASH: Rituxan Maintenance for Follicular Lymphoma

Sometimes ASH or ASCO or some other lymphoma-nerd conference is kind of a dud -- nothing really new or exciting to be discussed (at least, nothing I find exciting, which is what really matters).

This year's ASH conference is an exception. There's some good stuff that's going to come out of it, and as we get closer to the actual conference, we're going to see lots of press releases from research centers and drug manufacturers touting the good things that they reported on. I try not to get too optimistic about things. I'm all about hope, but hope, by definition, always contains just a little bit of doubt. If we were really sure of something, we wouldn't need to hope.

So read everything I say as optimistic realism.

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I predict that this particular paper is going to get a whole lot of discussion in the weeks ahead. It's called "Updated 6 Year Follow-Up Of The PRIMA Study Confirms The Benefit Of 2-Year Rituximab Maintenance In Follicular Lymphoma Patients Responding To Frontline Immunochemotherapy." The study is being led by Dr. Gilles Salles from Lyon, France. At the conference, this session is being held in La Nouvelle Ballroom AB at the Ernest N. Morial Convention Center. I've never been to this Convention Center, but I've been to enough conferences to know that the "ballroom" talks, especially when the ones that they take out the room divider for (it's in ballroom "AB," not "A" or "B"), are expected to attract a whole bunch of people.

Not surprising, given the topic -- Rituxan Maintenance. The PRIMA study (it stands for Primary RItuximab and MAintentance) is the major study of Rituxan Maintenance, and it is taking place in mostly European Study Centers (over 200 different hospitals and research centers in 25 countries). As the title of the paper indicates, it has been going on for almost 10 years now.

Here are the basics of the PRIMA study:  It looked at 1217 Follicular Lymphoma patients who were given one of three chemotherapies along with Rituxan (The chemos were CHOP, CVP, or FCM, which is a Fludarabine combo).  Of those patients, 1019 has a partial or complete response to the chemo + Rituxan combo. These were assigned to one of two arms: 505 patients were given Rituxan Maintenance; 519 got no further immediate treatment.  The R-Maintenance consisted of a dose of Rituxan every 8 weeks for 2 years. The first major update for the study was published in The Lancet (a major British medical journal) in 2010: after 36 months, Progression Free Survival for the R-Maintenance group was 74.9%; for the other group, it was 57.6%.  The conclusion: R-Maintenance works.

Now, the important thing to remember is that PRIMA is not the only study of R-Maintenance (though I believe it is the largest).  Other studies have shown less success, or at least less dramatic benefit. Lymphoma Rock Star Dr. Bruce Cheson offered a nice summary of some of these studies after last year's ASH conference. The basic complaint: still not enough evidence that the large number of doses of Rituxan is worth the expense, since there appears to be little Overall Survival benefit to R-Maintenance.

So now we have this year's ASH presentation. It reports on those same 1019 patients, but with three additional years of data. Here's the upshot: After 73 months (a little over 6 years), the Progression Free Survival rate for the R-Maintenance group is 59.2%, and for the other group, 42.7%. That's down some from 3 years ago, but that's certainly to be expected. The key number is the difference between the two groups. It has stayed roughly the same -- about a 17% difference. And the difference was even bigger for older patients (doesn't define what that means), female patients, and those with lower FLIPI scores.

Three other important points: 1) there seems to be no difference in the two groups for rate of transformation (which seems really small, though I need to look into that more); 2) there is no difference in Overall Survival (around 88% after 6 years); and 3) when patients did need a second treatment, there was no difference in the effectiveness of that treatment (in other words, the R-Maintenance didn't make the treatments less effective).

It will be interesting to see how people respond to this paper. It certainly does make a case for the effectiveness of R-Maintenance after chemo. But, as Dr. Cheson pointed out last year, there are some other studies that call into question whether r not it's worth it. My guess is the lymphoma community is going to be split: those who already believe that R-Maintenance is the way to go will praise it; skeptics will call on us to wait until some of those other studies (like the RESORT study) also present longer-term results, for comparison.

Or, maybe this will be enough, and we'll have some consensus that R-Maintenance is the way to go. (History, however, suggests that we will still be debating this next year. After all, the superior numbers for Bendamustine haven't stopped lots of oncologists from preferring R-CHOP as a first treatment.)

I'm kind of looking forward to what happens next.

I'll have something else from ASH in a few more days.