Transcript: Carla Casulo, MD: The National LymphoCare Study was a very large prospective observational study that was conducted many years ago, and it involved patients who were enrolled from a number of different sites: community sites, academic sites. It enrolled over 2000 patients.

The nice thing about the LymphoCare Study is that it actually gave us a wealth of information about how follicular lymphoma is approached in the United States. How is it treated? What are the patterns of care? That study is what my colleagues and I analyzed to better understand at what point relapse affects survival. We observed that about 20% of patients will consistently have disease recurrence, no matter what type of treatment they get.

The question was, does that impact their survival in any way? We took patients treated with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], and we divided them into those who had early progression, or what we now call POD24 [progression of disease within 24 months], and those who did have relapse within 24 months.

We found that if a patient with follicular lymphoma treated with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] relapsed within 24 months, they had a much less favorable outcome compared with those who didn’t. That’s what we now call the early progressor group, or the POD24 group. There’s a different way of defining that early therapy failure, but the take-home point is that these patients do much more poorly. Their overall survival at 5 years is only 50%, compared with patients who didn’t have early recurrence, whose survival was 90%.

If you think about follicular lymphoma, 50% survival at 5 years is actually quite low. Those are numbers that we would expect with much more aggressive disease. Someone who has an overall survival of 90% is much more in keeping with what you’d expect for this very indolent disease. What we really established is that this is a high-risk group of patients. We don’t really know why they relapse early. Some of these patients have early transformation. Some of these patients acquire different mutations. That is actually being studied very robustly worldwide, but what we do know is that they don’t do well. That was the biggest and most important contribution from that analysis.

That has been validated by several other groups around the world, including another group I was a participant in, called a FLASH [Follicular Lymphoma Analysis of Surrogate Hypothesis] data set, and that looked at validating the early relapsing entity as a true marker of poor outcome. That involved over 5000 patients with follicular lymphoma treated with a variety of treatment strategies. The same thing emerged, that if they relapsed early, no matter what they got, they still did poorly, compared with if they relapsed after 2 years.

It has impacted treatment in a big way, because from that study, many other subsequent studies have gone on to see whether drug A, B, or C works in the POD24 group. When you do a study in relapsed follicular lymphoma, you technically enroll any patient with relapsed disease if they need to be treated. Now, what studies are looking at are subsets of those trials—subsets of patients with early relapse—to see, does this treatment actually work in patients with early relapse? In fact, most have demonstrated that there is a benefit to many treatments in this space. A lot of them are novel treatments, like lenalidomide and some of the PI3 kinase inhibitors. I think that this a big emerging area.

The other thing is, the SWOG 1608 study is a large, cooperative national randomized study looking at this particular population. What this population of patients—this early relapsing group— is teaching oncologists and helping us to better understand is, what are treatments that could work for them? What are better treatments, and how can we bring that curve up from 50% and make it better?

Transcript Edited for Clarity