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Winter Stresses the Importance of Identifying Risk Status in Follicular Lymphoma Patients

Shannon Connelly
Published Online:2:34 PM, Thu January 18, 2018

Jane N. Winter, MD
The vast majority of patients diagnosed with follicular lymphoma will do well on therapy and have overall survival (OS) rates measured in decades. However, investigators are beginning to identify a portion of patients with follicular lymphoma, about 20%, who will progress within the first 2 years on therapy. Being able to identify this higher-risk group of patients upfront, and finding alternative treatment approaches for this group is key in progressing the field, according to Jane N. Winter, MD.

“There is this 20% of patients who have a dismal prognosis and we don't yet have a good way to identify them from the start. We are caught with waiting until these patients declare themselves, and then trying to identify new strategies for them,” Winter says.

In an interview with Targeted Oncology, Winter, professor of medicine, Division of Hematology/Oncology, Feinberg School of Medicine at Northwestern University, discussed recent updates in the field of follicular lymphoma, the importance of finding ways to identify patient populations, and challenges that still lie ahead.

TARGETED ONCOLOGY:  What are the most recent updates in the field follicular lymphoma?

Winter: Follicular lymphoma is a rapidly changing field. We are seeing a much better understanding of the disease, prognosis, and clinical behavior. More recently, we have new evidence showing that the majority of patients will do very well, but we are starting to identify one-fifth of patients who will do poorly. These are patients who progress within the first 2 years. These patients are destined to have a 5-year OS of only 50%, in contrast to others who will have an overall median survival measured in decades. This is something I always stress to my patients when they first see me. There is this 20% of patients who have dismal prognosis and we don't yet have a good way to identify them from the start. We are caught with waiting until these patients declare themselves, and then trying to identify new strategies for them.

Going forward, we need to be able to pick them out from the start, but we also need alternative approaches for these patients. The others are easy, for the most part. I like to use the metaphor of a marathon rather than a sprint. For that 20%, we're under great pressure to identify new options for them. The others do well regardless of what we do, and that is why it is so difficult to show any intervention improving OS. Those patients generally progress, respond, progress, and we have the pleasure of seeing them for many years.

TARGETED ONCOLOGY:  What novel agents or combinations are being studied right now that you find particularly compelling?

Winter: I think immunotherapy is the most exciting area in general, not just for follicular lymphoma, but also for large cell lymphoma. There is very little data on CAR T-cell therapy in follicular lymphoma, but we know follicular lymphoma to be one of the most immunologically driven lymphomas. We have known that for many years. We know that there are some patients who have spontaneous remissions. We know that there is a graft-versus-lymphoma effect. We also know that there are different genetic profiles that can identify those that have different immunoreactive cells in the microenvironment that change the prognosis.

It should be no surprise that immunologically-based therapies, such as checkpoint inhibition, are now showing some excellent preliminary results. A group from MD Anderson has showed that combining pembrolizumab (Keytruda) with rituximab (Rituxan) is excellent. It was very preliminary data presented at the 2017 International Conference on Malignant Lymphoma biennial meeting in Lugano, Switzerland, but very exciting with very high response rates.

Also, CAR T-cell therapy is early on for follicular lymphoma in comparison to large cell lymphoma where [there is already an approval for axicabtagene ciloleucel in certain types of large B-cell lymphomas] and what we hope will be an exciting future. There is a lot to be done with CAR T-cell therapy. 

It's amazing that we can take patients with relapsed and refractory disease and that some of those patients can be cured. Improving those numbers is very important. I personally have patients who have failed to respond to CAR T-cell therapy. We need to improve the response rate, which is only about 40% to 50%. There are a lot of places to go and things to do that hopefully will really make this a very effective therapy. 

I think immunotherapy is where we are seeing the most exciting advances. It's amazing, because for so many years people have worked in these areas without seeing much in the way of progress. It is finally coming into its own and that is very rewarding. Those who have been persistent need to be congratulated for their persistence, because there are many naysayers out there who felt that it is not going to be.

TARGETED ONCOLOGY:  What other challenges exist in the field?

Winter: We have not been able to select patient populations for particular therapies. We have not really identified different populations for different therapies as of yet. We have a lot of tools, but we do not really know how to use them. Our tool box is getting fuller and fuller, but we don’t yet know how to combine them, sequence them, and then think outside the box of using them appropriately. This is not to say we shouldn't be finding new tools—that is the highest priority. In large settings, we have tried identifying patient populations appropriately. We have tried a lot of that in large cell lymphoma thus far and haven't been able to make the headway we would like in that disease. 

TARGETED ONCOLOGY:  What is the take-home message from your talk for a community oncologist?

Winter: I would like to say 3 things. One is to remember that for the vast majority of patients, survival is measured in decades. I love that and like to tell my patients that. Number 2 is to remind them that within that larger population, there is that 20% that we don't yet know how to identify until they progress and prove refractory within the first 2 years. Evaluating patients and knowing whether people have shown evidence of progression or relapse within that time period is perhaps more important than it was previously because you need to identify those patients. Thirdly, I like to point out the early-stage data that was presented by an international consortium at the International Conference on Malignant Lymphoma underscoring the value of involved site radiotherapy for early-stage disease, particularly and perhaps exclusively when it is stage I by PET, so that you can identify this patient population. This is a better defined patient population, a smaller subset of all those who you might previously have thought were early-stage, because PET upstages a significant percentage of patients. You do the PET and you discover that they have more advanced disease than you thought. This continues to be a promising underutilized strategy that has the potential for cure. We don't have many options that cure patients with follicular lymphoma, so I'm still a big proponent, and I know it's a very underutilized modality in the United States. 
 

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