R-Squared: 10 Year Follow-Up

The medical journal Blood published the results of a 10 year follow-up of R-Squared. The results aren't surprising (they are positive), but it's the larger content that it more interesting to me.

The article is called "Lenalidomide plus rituximab for previously untreated advanced follicular lymphoma: the 10-year RELEVANCE trial analysis."  As a reminder: R-squared is the shirt name for the combination of Rituxan and Revlimid (also known as Lenalidomide). R-squared was the first non-chemotherapy treatment that was shown to be as effective as traditional immunochemotherapy (like R-CHOP or R-Bendamustine), though it had a different set of side effects that were just as serious. The AUGMENT trial and the MAGNIFY trial led to R-Squared being approved for FL patients who had already received treatment. 

The RELEVANCE trial involved patients who had yet not received any treatment.  The original trial was large -- 1030 patients. More importantly, it is a two-arm study, so it shows a direct comparison between patient receiving R-Squared and those receiving immunochemotherapy. In 2022, I wrote about a 6 year follow-up study.  As I said then, "The results of the study showed that R-Squared remained just as effective after 6 years as it had been up to that point. The Progression-Free Survival (showing that the disease didn't get worse after 6 years) was 60% for R-Squared and 59% for R-chemo. Overall Survival was 89% for both groups. The transformation rate (the slow-growing FL turned into a fast-growing cancer) per year was 0.68% for R-Squared and 0.45% for R-chemo, and secondary primary malignancies (patients developed a new, different cancer) was 11% for R-Squared and 13% for R-chemo. There are some other statistical comparisons as well, but they all say the same thing -- R-Squared is as effective as R-chemo, and as safe."

So would R-Squared hold up as well after 10 years? Yes it does.

The median Progression Free Survival after 10 years was 110.6 months for the R-Squared group and 102.8 months for the Immunochemotherapy group.  The rate of patients with a 10 year PFS was 46.4% for R-Squared and 46.6% for chemo. Almost identical. The median Overall Survival and the median Time to Next Treatment were not yet reached in either group. (Remember that the "median" means the middle of a group, so if the median wasn't reached, it means that more than half of the group has survived and has not yet needed treatment after 10 years). The 10 year Overall Survival rate was 82.4% for the R-Squared group and 81.1% for the chemo group. The 10 year Time to Next Treatment rates were 62.2% and 66.3%. Only 9 cases of transformation occurred (3 with R-Squared and 6 with chemo). 

Comparing the 6 year follow and the 10 year follow up, it's not surprising that numbers went down after 4 more years, but more importantly, the numbers comparing the two treatments were very similar. As the researchers say, R-Squared continues to be an alternative to immunochemotherapy for untreated FL patients.  

The researchers also said this was 10 year follow-up was always part of the plan for the study, and that it would be their final analysis.

Here's what I mean when I say it's interesting in a larger context.

A few months ago, researchers published a 15 year follow-up of R-CHOP and used some statistical analysis to show that about 40% of patients in the study were probably cured. One of the big outcomes of that article was the idea that we now have a new benchmark -- other long-term studies are going to be challenged to do the same kind of statistical analysis to determine what their cure rate was. In other words, the RELEVANCE study shows that after 10 years, there isn't a whole lot of difference between R-Squared and immunochemotherapy, in terms of effectiveness. But can R-Squared match the 40% cure?

We're not getting that information here (or in the 15 year follow-up of R-Squared in the MDACC trial that was published in February) because that wasn't part of their plan. I don't know enough about statistical analysis of clinical trials to know if a biostatistician can come in later on and look at the data for a trial and make that same kind of call. But it will be really interesting to see if that kind of analysis starts showing up at conferences like ASCO and ASH and in medical journals. I'm certainly all in favor of it. I have a complicated relationship with the word "cure" after 18 years, but more studies that use that analysis and use that word might change my mind.

In the meantime, though, it's great to see long-term data of any kind to show that we have some choices. Given our own individual circumstances, there's more than one treatment available for us that will give us a chance at a good, long Overall Survival. That's some very happy news.