R-Squared: 10 Year Follow-Up

The journal Blood Advances just published an article called "Six-month rituximab-lenalidomide regimen in advanced untreated follicular lymphoma: SAKK 35/10 trial 10-year update." It says some excellent things about R-Squared, as well as about Rituxan.

The article reports on a phase 2 clinical trial conducted by researchers in Switzerland. It compares R-Squared (Rituxan plus Revlimid, also known as Lenalidomide) to straight Rituxan as a first treatment for Follicular Lymphoma patients. There were 154 patients in the trial, with grade 1 to grade 3A FL. Half were given Rituxan and half were give R-Squared.The data looks at results of the trial 10 years after it started -- a very long time for cancer research.

The study found that overall, the R-Squared combination worked better than the Rituxan.  The primary endpoint (the most important outcome being measured) was Complete Response at 6 months and then at 30 months. By comparing the two time intervals, researchers can get a sense of Duration of Response -- how long the response lasted.

The R-Squared combination had a longer duration of response. The median was not yet reached after 9.5 years (meaning more than half of the patients continued to have a response), while the duration of the Rituxan group was 3.2 years (still very good).  The median Progression Free Survival was also very good for the R-Squared (9.3 years versus 3.2). 

As far as efficiency goes, the R-Squared clearly won that comparison.

As for safety, things were a little bit different. There has been much research on the two types of treatment already, so the side effects are well-known. As expected, R-Squared tends to have more side effects than Rituxan (since there are two treatments being combined, each with its own set of side effects). No new side effects were noticed, and the R-Squared side effects were "manageable." Each of the groups reported a similar number of deaths after 9.5 years, with 15 in the R-Squared group and 14 in the Rituxan group, though one of the R-Squared deaths came from sever side effects. 

It's important to note here that deaths are from any cause, not necessarily from the disease or the treatment, with the exception of the one that was mentioned.

Along those same line, the Overall Survival of both groups about the same after 9.5 years: 77% for the R-Squared group and 78% for Rituxan. That's also not a surprise. The Overall Survival of most treatments for FL is about the same. It's very hard to show a survival benefit among treatments. If there was a big difference, we'd probably all be gravitating toward that treatment instead of arguing over which one was the right one.

And that's important to note, too. If the goal is to live as long as statistically possible, then there are lots of choices. So other factors have to be considered when choosing a treatment. If the goal is to avoid side effects right now and sacrifice a long PFS (meaning you'd need to get a second treatment sooner), that's different from tolerating harsher side effects now for the chance at a longer time until another treatment. that's why it's important to talk things out thoroughly with your oncologist before choosing a treatment. We all have different goals.

It's important, too, to remember that all of these numbers are medians. That means whatever they are measuring, the median is the exact middle. So if the median PFS for Rituxan is 3.2 years, then half of the patients had their disease progress before 3.2 years, and half went longer than 3.2 years. I've known people who didn't respond at all to Ritixan. And then there's me -- I had Rituxan 15 years ago and I haven't needed treatment since.

It's all very complicated, isn't it? 

I wish that wasn't how it is, but that's what we're dealing with. As I said, the best thing to do is keep up-to-date, including regular conversations with your oncologist. You have choices. It's best of they are informed choices.