R-Squared 15 Year Follow-Up

A couple of weeks ago, a reader named Johnatan sent me a link to an article from Blood and asked if I'd seen it yet. I had not seen it -- it came out while I was reading all of those ASH abstracts. But it's worth taking a look at.

The article is called "Phase II Trial of lenalidomide plus rituximab (R2) in previously untreated follicular lymphoma: 15-year follow up data from MDACC Trial." 

It's an important study for a couple of reasons. 

First, it's always great when we get long-term data about a treatment. And 15 years is a long time. I love the idea that this study was starting when I was just out of treatment, and I had no idea it was even happening. Just think about how many amazing clinical trials are happening right now that we won't even hear much about for a few years.

But that 15 year follow-up is great. We always assume that a new treatment will continue to be good, but it's great to see the actual data that shows it.

Second, a long-term study of R-Squared (Lenalidomide + Rituxin) is especially important because it seems that R-squared is becoming the base treatment for lots of new combinations. In other words, researchers used to say "What would happen if I added thing new thing to CHOP or Bendamustine?" Now they're saying "What would happen of I added this new thing to R-Squared?" Just look at the excitement over Epcoritimab. It's not on its own -- it's in combination with R-Squared.

The original study that the article discusses was a phase 2 clinical trial at MD Anderson Cancer Center. It involved 79 patients with Follicular Lymphoma who had not yet had treatment. The participants were broken into two groups, one receiving six cycles of the combination and one receiving 12 cycles. The participants had a range of risks, based o FLIPI scores. The Overall Response Rate was 99%, with the Complete Response Rate at 87%.  Even with the long-term follow-up, a large number of patients could not be evaluated, with almost half not showing up for clinical visits after a while, particularly during the Covid pandemic.  

Despite that, the long-term follow-up numbers look great. The median Progression-Free Survival (the time it took from diagnosis for the disease to progress) as 16.5 years, with 61% of patients having their disease not progress for 10 years. At 30 months, 76% of the patients were in Complete Response. The patients who were in the group that received 12 cycles of the treatment had a longer median 10 year PFS than the 6 cycle group (75% vs 70%). And while 9 of the patients being followed died during the 15 year follow-up, only one was for a cause related to Lymphoma. The 10 year median Overall Survival was 95%. There were 11 patients who experiences POD24, progressing with 24 months, and 5 whose disease transformed, with the time to transformation ranging from 9 months to 15 years).

I would have loved to tell you that every patients was doing great after 15 years, but that's not how things work, unfortunately. But I can tell you that these 15 year follow-up numbers are excellent. A 10-year median Overall Survival of 95% is kind of amazing. 

So it's easy to see why R-Squared is becoming the base treatment for other combinations. I have still not seen numbers that show that R-Squared has become kind of the default treatment for patients (the most recent one I can think of had R-Squared being given to less than 10% of FL patients).  But things change over time. 

Thanks, Johnatan, for sharing the link to the article. I'm always happy to receive things like this, in comments or by email. Always feel free to contact me if you think I can be helpful, and I'll do my best to help.