Yet More on R-Squared

The Journal of Clinical Oncology published a commentary on the article that I wrote about in my last post. The research article discusses the AUGMENT trial. The commentary is called "Augmenting Indolent Lymphoma Treatment Options With the Combination of Lenalidomide and Rituximab." It's written by Dr. Paul Barr from the University of Rochester.

First of all, I love a good pun in a medical journal title.

Second, and more importantly, Dr. Barr gives a little more context to where the R-squared combination might fit in to the Big Picture for Follicular Lymphoma treatment.

As Dr. Barr points out, Follicular Lymphoma treatment has become more successful since Rituxan was introduced. I have said often that, when I was diagnosed in 2008, I read the the median survival for FL patients was 8-10 years. (That was probably a low estimate taken from an older study.) As Dr. Barr points out, estimates now put the median survival at closer to 20 years. People diagnosed in their 60's (the age when most people are diagnosed) are living to the time when the general population is living. That's excellent news.

However, there is a subset of the FL population that doesn't do as well. For about 20% of patients, they receive immunochemotherapy (something like R-CHOP or R-Bendamustine), and the doisease comes back within 24 months. This group has a lower median Overall Survival than the other 80%. (Though it's important to note that neither of those groups is ever guaranteed anything -- a long life or a short one -- because statistics are about large groups, bot the individuals within those groups. Take a second to remind yourself about that.)

The people in that group might do well with a treatment that acts differently from the Rituxan or the chemo that they have already had. R-Squared might be a choice for them. While it contains Rituxan, like most immunochemotherapies, it's the other R, the Revlimid (or Lenalidomide) that is different. It's an "immunomodulatory" treatment. Basically, it works in the bone marrow, where blood cells are formed -- it encourages good cells and helps to kill off bad cells. (There's more to it than that, but that's the basics.) And when Lenalidomide is combined with Rituxan, they work together very well.

The RELEVANCE trial involved patients who had not yet received treatment. Results showed that, for this group, it worked just about as well as immunochemotherapy. But it wasn't better, so it probably won't replace immunochemo as the first choice for many patients.

The AUGMENT trial, though, looked at patients who did receive treatment. The results of that trial were good. The trial compared R-Squared to just Rituxan (no chemo added), with good results. Dr. Barr is guessing that both treatments have a place. For patients who have a relapse, but have low tumor burden, Rituxan might be a good choice. But for patients who relapse and have a more aggressive disease, R-Squared might be a good choice.

In the end, though, with a good number of choices available to Follicular Lymphoma patients, what we really need is some way to know which treatments will work best in which situations. That work has been happening, but the results are coming as quickly as we would like. Perhaps the focus right now should be on that 20% who relapse after 24 months, since their situation is more urgent. The rest of us can do OK with what is currently available.

I've been writing about R-Squared a lot lately. That's because it's been in the news a lot lately. But all of this news kind of confirms for me that all of the excitement about R-Squared for the last few years has probably been justified. Assuming we see approvals from the FDA and other regulators, my guess is that we'll see a lot more patients being treated with it, and it will become as much a part of our conversations as Rituxan, R-CHOP, and Bendamustine. Just a guess, but if oncologists are excited about it, that will probably mean they recommend it more to patients. So be prepared -- know your options when the time comes.