Reducing Early Disease Progression in Follicular Lymphoma - Episode 3

GALLIUM Exploratory Analysis: Managing Disease Progression

Timothy Fenske, MD, MS:Although we have a number of effective treatments for follicular lymphoma, the reality is that the majority of patients will eventually relapse with their disease. Really, the only treatment that’s been definitively shown to be curative for follicular lymphoma is hematopoietic stem cell transplantation. There we have patients who have sustained remissions for 10 or 15 years, but this treatment is not an option for all patients, and it comes with a significant amount of risks.

All the other treatments that we tend to give for follicular lymphoma, while effective, are not thought to fully eliminate the malignant clone. And while it can be a very slow-growing or indolent process, given enough time we think that this will reappear in most patients.

A really important area in follicular lymphoma has become this idea of early progressors. There was an important study from the LymphoCare database that initially shed light on this. In the LymphoCare study, they defined early progressors as people who had a recurrence of their disease within 2 years of their diagnosis. Subsequent to that, there have been a number of studies looking at this—the incidence of early progression.

Most of those studies have defined early progression as progression within 2 years of the start of your first antibody-chemotherapy combination treatment. There’s a slight difference in terms of how those are defined. Regardless of how we define it, we’ve seen this in about 20% of patients. The LymphoCare study showed that number to be about 20%. In more recent studies, like the GALLIUM study, for example, that number has come down. I think 1 of the important findings in the GALLIUM study was that we saw early progression in only about 17% of patients treated with the rituximab-chemotherapy combination, and it was 10% in the obinutuzumab-chemotherapy combination. That 10% rate of early progression is the lowest rate I’ve seen in studies that have been published to date.

The reason that early progression is such an important factor for follicular lymphoma patients is because in the LymphoCare study and subsequently seen in several confirmatory studies, patients who have early progression have a subsequent survival somewhere in the 30%-to-50% range at 5 years. Whereas if you don’t have an early progression event, 90% of those patients are alive 5 years later.

This is a really big discriminating factor, particularly when you consider that when these patients are diagnosed, we’re telling them that we think they could have a life expectancy of 20 years or longer. And now if they have an early progression event, we’re looking at maybe only a 5-year survival on that horizon.

That’s a big change, and I think we react to that now in that we consider those patients to be candidates for stem cell transplant. This is 1 group of patients for whom we’re really kind of focused on when considering transplant. I think if you’re a younger patient with follicular lymphoma, those patients don’t really want to have to have that conversation about transplant. One way to prevent the need for that conversation is to try to reduce their risk of having an early progression event.

In the GALLIUM study, there was an exploratory analysis, which was recently published, looking at the rate of early progression between the 2 study arms. This was an exciting result in that in the rituximab-chemotherapy arm, they saw about 17% of patients having an early progression event, which is similar to other studies using rituximab-chemotherapy combinations. Whereas with the obinutuzumab-chemotherapy arm, that early progression event was about 10%. The difference in terms of early progression was seen even at the 1-year mark, and we know that patients who progress within 1 year have a particularly poor outcome. I think this is 1 of the few interventions we can think about that has been shown in a prospective trial to reduce the risk of early progression, which for younger patients—in particular, with follicular lymphoma—is a very important endpoint.

Transcript edited for clarity.