Improved Outcomes for Transformed FL

The journal Cancer Medicine  published a very interesting article lest month called "Outcomes of the transformation of follicular lymphoma to diffuse large B-cell lymphoma in the rituximab era: A population-based study." It describes a large research study that compared the outcomes for patients who were diagnosed with Diffuse Large B Cell Lymphoma (DLBCL), an aggressive type of Lymphoma, with those who were diagnosed first with Follicular Lymphoma and whose disease then transformed to DLBCL. There's lots of interesting data here, but the most important is this -- in the last 20 years, outcomes for FL patients with transformed lymphoma are greatly improved.

It is important to note that this is a "population study," meaning the researchers didn't look at individual patients. Instead, they looked at a large database called the SEER (Surveillance, Epidemiology, and End Results). You're probably in it -- oncologists upload anonymous data into the SEER database so this kind of large study can be done. Population study look at trends, rather than individual patients. But because they are looking at large numbers of patients, the results can be very interesting.

For this study, the researchers were interested in patients with transformed FL who were diagnosed between 2000 and 2020. This time period is known as "The Rituxan Era." Rituxan was approved by the FDA in 1997, and there were big improvements in FL patient outcomes once Rituxan started getting mixed with traditional chemo, and then with other treatments. As the researchers note, small studies focused on transformed FL are inconsistent in what they reveal, so they thought a large study like this would be helpful.

And it is indeed large. The researchers found 50,332 FL patients in the database who were diagnosed in that 20 year period, along with 95,933 patients who were diagnosed with primary DLBCL (in other words, they didn't have FL first). Of those 50,000+ FL patients, 1631 had disease that transformed. 

That in itself is very significant to me. When I was diagnosed (in 2007), I read in many places that as many as 50% of FL patients would end up with transformed disease, which was alarming to me. Over time, in the small studies that I read, the numbers would usually come as closer to 15 or 20%. That's slightly less worrisome. But in this large study, only 3.2% of FL patients transformed to DLBCL. That is, obviously, a significantly smaller number. 

(I'm not suggesting the old research was wrong, or the new research is wrong, or that transformation is no longer a big deal. Just that the smaller number is very surprising to me.)

In fact, it's important to note that one of the things the researchers make clear is that transformation has a serious impact on Overall Survival. For patients with transformed disease, the OS rate at 10 years was 56.6%, with a median survival of 137 months (a little over 11 years), with a range of 2 months to 21 years. For patients who did not have transformed disease, the 10 year OS was 64.8%,  with a median survival of 194 months (about 16 years), with the same range of 2 months to 21 years. So clearly, transformation is still a big deal.

But the larger point they're trying to make still holds true --  compared to the time before Rituxan, outcomes for transformed FL are better. 

A few other interesting bits:

• Patients who had received Radiotherapy or who Watched and Waited had better outcome after transformation than those who received traditional chemotherapy or a combination of chemo and radiation. (they don't get into why this might be so, but my guess is that it has less to do with the treatment itself and more to do with how aggressive the disease was before transformation. FL patients who watch and wait tend to have less aggressive disease; those who get chemo tend to have more aggressive disease. All of that is entirely my own, non-expert guess.)
• Patients whose disease transformed soon after their FL diagnosis (within 18 months) tended to do better than those with later transformation (after 18 months). I wonder if this had to do more with how long it took to discover the transformation, rather than the actual transformation. Again -- my non-expert guess.
  
• There are more options now for treating transformed FL, obviously. The recommendation used to be a Stem Cell Transplant. That's still an option, but no longer automatic, especially as more FL patients have traditional chemo "reserved" as a later possibility.

It's fascinating to me that, even 16 years after I was first diagnosed, we still have lots of unanswered questions about transformation -- and about so many other aspects of Follicular Lymphoma.  But despite the lack of answers, we are still seeing overall improvement as a group. And that's worth celebrating.