R-Squared in Untreated Follicular Lymphoma

More evidence that R-squared is a very good option for many Follicular Lymphoma patients.

R-squared, as you probably know, is the combination of Rituxan and Revlimid (also known as Lenalidomide). It was approved by the FDA in May 2019 for previously-treated FL patients. It was big deal -- it showed that it was possible for a non-chemotherapy treatment to be as effective and safe as traditional chemo. If you've been reading Lympho Bob for a while, you know I've been tracking it for a long time. For years, lymphoma specialists have been saying R-squared could be a game-changer.

So while it has been approved for previously-treated FL patients, there is now more evidence that it is effective for untreated Follicular Lymphoma patients, too.

 A recent article in the journal Blood Advances, called "Lenalidomide/rituximab induces high molecular response in untreated Follicular Lymphoma: LYSA ancillary RELEVANCE study," makes this clear.

The research describes a smaller part of the large clinical trial known as the RELEVANCE study (which I have written about a few times).  This trial was a comparison of R-squared and Rituxan + chemo, in FL patients that had not yet had treatment. Half the patients were given R-squared, and half were given R + chemo.

A smaller group within the RELEVANCE trial were part of an MRD study. MRD stands for "Minimal Residual Disease." It's the idea that something like a CT scan won't see the smallest little bits of cancer that might remain in a patient's body after treatment. Looking more closely at DNA samples will show if all of the cancer is really gone, more that what a scan might show.

So in the research described in the article, 222 with a particular genetic issue (a BIOMED-2–detectable BCL2-JH translocation) were analyzed. In other words, these patients had a specific problem with their DNA that caused the Follicular Lymphoma. That's important -- successful treatment would mean that the cells with that DNA problem would be wiped out. If a blood test or bone marrow test showed some of those cells were still around, then the treatment didn't result in a true Complete Response. If it did, it resulted in what's called a Complete Metabolic Response, or CMR -- no messed up DNA in any of the cell samples they took.

These 222 patients were given the treatments in the study (117 were given R-squared and 90 were given R + chemo -- that doesn't add up to 222 but that's either because some patients didn't complete the study or I'm just really n\bad at math).

Complete Metablic Response at 24 weeks was achieved in 105 of the 117 R-Squared patients (90%), and in 70 of 90 R + chemo patients (77%). That's a great thing for R-Squared.

Just as importantly, the patients who had a CMR at 24 weeks were more likely to have a long-lasting response to the treatment, whichever treatment they had.  Patients with a CMR had a 3 year Progression  Free Survival of 84%, while those who didn't have a CMR (they still had some cells with the messed up DNA after 24 weeks) had a PFS of just 55%.

So two important results: more evidence that R-Squared is effective in Follicular Lymphoma patients who had it as their first treatment, but also, more evidence that CMR is a good predictor of how long a treatment will last. Knowing that a CMR wasn't achieved might mean that Maintenance might be a good idea, or that a salvage therapy (a new treatment right after a partially successful treatment) might be necessary.

Overall, some good news for those who are considering R-Squared, but also good news for all of us that want to know how well a treatment might have worked.