Expert Discusses State of Follicular Lymphoma Treatment in 2017

Nathan Fowler, MD

Over the past 25 years, new regimens for follicular lymphoma have led to better overall survival; however, outcomes often dramatically vary among patients receiving the same standard treatment, such as R-CHOP.

“Some patients with the same therapy could have a median survival around 3 to 5 years, whereas others have a median survival of 14 years,” said Nathan Fowler, MD.

The Follicular Lymphoma International Prognostic Index (FLIPI) has contributed to determining which groups of patients will likely respond more successfully to treatments, but the scoring system has difficulties predicting the outcome for individual patients.

OncLive: Can you discuss the current management of high-risk follicular lymphoma?

In an interview with OncLive, Fowler, an associate professor of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, discussed the current management of high-risk follicular lymphoma and ongoing developments in the field.Fowler: We've known for quite some time that patients with follicular lymphoma behave differently when treated with the same therapy. Patients can get a standard therapy, such as R-CHOP and have dramatically different outcomes. In fact, some patients with the same therapy could have a median survival of around 3 to 5 years, whereas others have a median survival of 14 years.

The field has been moving to identify those patients with different types of biologic and clinical factors. Several years ago, we developed the FLIPI score, which is a scoring system looking at 5 clinical factors in patients before they get treatment. It turns out that the FLIPI score does predict patients that have positive or negative outcomes to treatment. As this has advanced over the past 10 years, other scoring systems have been developed. There is now the m7-FLIPI as well as immunohistochemical standing, which has the ability to predict some subgroups of patients who will do poorly.

About 2 or 3 years ago, groups from the United States were looking at patients with follicular lymphoma to determine their outcome after initial therapy. They attempted to determine how long remission lasts and if early remission predicted a patient’s long-term survival. It turns out that if patients who receive R-CHOP progress within 2 years of treatment, they will have inferior survival compared to patients who have longer remissions.

There is also a group from the Mayo Clinic that looked at patients with follicular lymphoma and followed them after initial diagnosis. If they experienced progression within the first 12 months following diagnosis, they also tended to do poorly. This means that you can look at very early outcomes in these patients and predict long-term survival.

The next step is to design clinical trials focusing specifically on these high-risk patients and attempt to change the natural history of the disease. We need clinical trials to guide us as to how to treat these high-risk patients with the current agents available

There are a couple trials that have subsets of patients that were treated with any given therapy who fell into this high-risk category. Patients that are double refractory or alkaline or rituximab resistant have a 60% response rate when treated with bendamustine (Treanda). Idelalisib (Zydelig) which is approved for relapsed follicular lymphoma, also has response rates around 60% or higher in patients who are failing chemotherapy and rituximab. Lenalidomide (Revlimid) and other combination therapies similarly have response rates of 50% to 60% in this double refractory population.

When a patient is initially diagnosed, what are some of the factors that could predict whether they will have a worse outcome?

Finally, we should not ignore methods of autologous stem cell transplant. It's been clear that if you take a patient who is refractory to one line of chemotherapy, this does not necessarily predict long-term poor outcomes. In fact, retrospective data, looking at patients who underwent a transplant, suggested that even patients who had short remissions could experience prolonged survival. Around 60% of patients following autologous transplant will have a long-term remission. In patients who are initially diagnosed, we know that certain clinical factors do predict patients who have a worse outcome. The FLIPI scoring system can at least accurately predict the outcome of those groups of patients. The scoring system is based on hemoglobin, stage 3 or 4 disease, a number of nodal sites, the patient's age, and their LDH.

What types of clinical trials would be useful in further advancing the field of follicular lymphoma?

If a patient has 3 or more factors, they tend to do poorly following therapy with R-CHOP. However, there are individual patients within that group who can do well. It’s not perfect at predicting the outcome of individual patients, only as patients of a group.This is an exciting time for the field because we have a lot of new drugs that are very active. They have different mechanisms of action, meaning they’re not standard chemotherapy. These new drugs can target key components within this cell, as well as certain kinases, which may be overactive in certain subtypes of follicular lymphoma, and are potentially able to harness the power of a patient’s immune system.

In the next generation of studies, we would like to look specifically at the high-risk group of patients and randomize them to receive standard chemotherapy or different combinations of some of these new emerging agents. Hopefully, by intervening early with an alternative strategy of treatment, these patients will see an improvement in their long-term outcome.