ASCO Preview: Revlimid and Rituxan (R-Squared) for FL

As many of you know, the combination known as R-Squared has been on Lymphoma specialists' minds for a while. In those review articles and videos that I like to link to, they almost always mention the combination as something that they are excited about. The results of a phase III trial of the combination is being presented at ASCO.

R-Squared stands for Rituxan and Revlimid (also known as Lenalidomide).

The ASCO presentation is called "RELEVANCE: Phase III randomized study of lenalidomide plus rituximab (R2) versus chemotherapy plus rituximab, followed by rituximab maintenance, in patients with previously untreated follicular lymphoma."

Researchers are using the trial to do a direct comparison between two treatments. A total of 1030 were split into two groups. One group received the "standard of care" -- the kind of treatment most patients would receive if they were not in a trial -- immunochemotherapy + maintenance. In this case, that meant R-CHOP, R-CVP, or R-Bendamustine, followed by Rituxan Maintenance (every 8 weeks for about 2 years).

The other group got the R-Squared, followed by the same Rituxan Maintenance.

The results were very interesting -- the two treatments were very similar in their effectiveness, but with different side effects.

The primary endpoints (that is, the measurements the researchers would use to figure out of R-Squared was better) were Complete Response (how many patients had their cancer wiped out) at 120 weeks, and Progression Free Survival (how long it took for the cancer to come back, or get worse).

The CR for R-Squared was 48% to 55% (depending on who was measuring), with the Immunochemo CR was 53% to 58%. Very similar.

The PFS at 2 years for R-Squared was 84%/84%, while the Immunochemo was 87%/83%.
The PFS at 3 years for R-Squared was 77%/77%, while the Immunochemo was 78%/78%.

[There are two numbers for each because there are two groups looking at the results -- the researchers themselves, and then an independent group of experts. This makes sure that the researchers aren't  overlooking something because that would give better results. It's a sign that the researchers are taking the results very seriously and want them to be fair.]

The Overall Survival for both groups at 3 years was 94%.  [Only one set of numbers there -- you really don't need independent experts to check if someone is still alive.]

So while the effectiveness of the two treatments is virtually the same, the differences came in the safety -- they had different side effects.

Patients in the Immunochemo group had higher instances of neutropenia (low levels of a white blood cell that fights off infections) and of fevers associated with neutropenia. The Immunochemo patients also had a slightly higher incidence of developing secondary cancers (9%, versus 7% in the R-Squared group).

The R-Squared group had higher rates of cutaneous events -- skin problems.


A couple of comments, for what they're worth (coming from a patient and not a medical doctor or researcher).

First, I really like that the researchers stayed fairly neutral in all of this. They sum it all up in the conclusion as saying "R-Squared showed similar efficacy and a different safety profile to R-chemo." It would have been easy to hint that R-Squared was better here, or that it prevented a better alternative. The numbers don't say that, but lots of researchers kind of use language that would suggest it. (A report in Lymphoma News Today does that, saying the results suggest that R-Squared could replace chemo.)

I am certainly prone to being (maybe overly) optimistic. For me, as a patient, that puppy-dog-like enthusiasm comes off as charming. But for the researchers, neutral is better. So I really appreciate that they are presenting data and letting others make the judgements about what it all means.

Second, my guess is that others will indeed give a positive spin to the results. The abstract states that "superiority for R-Squared over R-chemo was not established for both co-primary endpoints." That's a technical term for the clinical trial -- the goal was to show that one was more effective than the other, and the results don't show that. they are just as effective as one another.

But in practical terms, being the same could mean being better. We'll see what people have to say next week, in those ASCO round-ups, but there are a lot of Lymphoma experts who think we are moving away from chemo, and a lot of Lymphoma patients who paralyzed by the word "chemotherapy." Any treatment that is not chemo, but does as good a job (whatever the side effects) will be really attractive to those groups.

I am really curious about how the Lymphoma community will react to all of this.

For me, despite the "non-superiority" and the "similar efficacy but different safety profile," I think it's good news. Puppy dog that I am, I think choices are good for us, and if this presents a legitimate choice, so much the better.

I'm sure we'll be hearing more about this in the next few weeks.