Current Treatment Landscape, Emerging Therapies for Patients With FL

Elizabeth A. Brem, MD, Assistant Professor, University of California, Irvine, discusses the current treatment landscape and new emerging therapies, such as chimeric antigen receptor (CAR) T-cell therapy, for follicular lymphoma (FL).

Transcript:

Dr Brem: Hi, my name is Liz Brem. I'm an assistant professor here at the University of California, Irvine.

Oncology Learning Network: Can you talk about the current treatment landscape for FL?

Dr Brem: The good news for FLs I think we have a lot of options.

Actually, I had some trainees in clinic with me this morning and was kind of discussing how (the approach) really is very heterogeneous. It depends a lot on the person in front of you, how much disease they have, how symptomatic they are. We do have patients who sometimes we can treat them with something as simple as 4 weeks of rituximab and they can go into a long-term remission, versus other patients where we might reach for other options.

There's still (a role) today for use of chemotherapy for FL, but this may eventually go the wayside of some other diseases where we are using less and less chemotherapy every year because we have other options.

OLN: Are there any key publications, approvals, or data sets of note that you would like to mention?

Dr Brem: I think it's helpful to remind people that rituximab, lenalidomide, or R2, is FDA approved for the treatment of FL. Those of us in the academic setting are aware of this and we use it relatively often.

I don't know if my colleagues who practice in the community setting are thinking about that therapy as frequently, but it is an available and FDA-approved option. One of the nice things about is it is time limited, and that's based on the AUGMENT study.

Of the more recent data people are getting excited about in FL is specifically looking at these things called bispecific antibodies. One end attaches to CD20 on the malignant B cell, the other end attaches to CD3 on the T cell.

This seems to be a particularly effective strategy in FL. Response rates are quite high. They vary depending on the dataset and which specific drug you are looking at, but every meeting there's more data coming out that gets people more excited about bispecific antibodies.

So, certainly be on the lookout. Those are going to change the treatment paradigm I think relatively soon.

OLN: What are the hot topics being discussed in the FL space that you are personally most excited about?

Dr Brem: One thing that people are starting to go back to is, we were always told and I always tell patients that this is an incurable disease.

That is why we do things like watch and wait strategies. We wait to treat people until it's bothering them, because to date, there's never been any data showing that if you treat people earlier, that they live longer.

But, history repeats itself and every few years or generation, people come back to these questions like this and people have said, "Well, things are different. We have more than chemotherapy. We have more than rituximab. We have bispecific antibodies. We have a CAR T-cell that is FDA approved in FL. Should we be rethinking that paradigm? Should we re-challenge this notion that treating people sooner doesn't change outcomes if we are selecting the right patients and using drugs that work completely differently than anything that have been tried in the past?"

So, I think people are starting to go back to that fundamental question of, "Is there a chance that with some people we could cure FL?"

I don't know what the answer's going to be. I don't know what the right study is going to look like, but people are starting to go back to that really fundamental question, which is huge for patients and kind of rethink this disease.

OLN: Can you go into the CAR T-cell therapy side of FL?

Dr Brem: It's new. I think the approval for CAR T-cell only came out within the last year. I think we're still trying to figure that out.

We have one CAR T-cell product that is FDA approved for FL, and that approval was fairly recent. It is based on a single arm phase 2 study.

That being said, the patients on that study did really well. Just pulling up the data from my memory, 91% of these patients did have a response. Now, did everyone have a complete response (CR)? No. For those who had a CR, how long is that going to be maintained? I mean, time will still tell, but certainly the couple of years of follow up we have so far are really exciting.

It is approved for people who have had at least 2 lines of therapy. Should that be line number 3? Should it be line number 4? There's going to be another study looking at CAR T-cell even earlier (as early as second line), so should it be even earlier than that line of therapy?

We're still trying to figure out who and when to refer to CAR T. As I kind of alluded to the other part of this is FL is such a heterogeneous disease. We know, for example, these patients who relapse within the first 24 months, this thing called POD24, that those patients don't do as well. There are actually now a number of studies particularly targeting that population.

You could hypothesize that maybe that population would be one that would be particularly likely to benefit from CAR T-cell therapy. Though, again, I'm hypothesizing that. I think as a whole, we're still trying to figure it out. There's the, "When to refer patients to CAR T? Who to refer to CAR T?"

There's of course the practical reality of this is not something everyone (has) eligible to them. It has to be given in certain centers, typically tertiary care centers who also do things like bone marrow transplant, and some patients either can't or will choose not to go to one of those centers. So, it's unfortunately a therapy that not all of our patients have access to, even though the data so far is very encouraging.

OLN: Are there any issues you have seen pertaining to patients getting FL treatment or diagnosis?

Dr Brem: In terms of (making sure you have the right) diagnosis, I think that's always key.

That's one thing that those of us who treat lymphomas are very hyper vigilant about, making sure to always get the right diagnosis, because sometimes it's hard to tell exactly which flavor of indolent lymphoma someone has. Sometimes you're even playing the game of is it high grade, or is it just the indolent lymphoma.

One challenge that maybe comes up more often with the low grade lymphomas than the high grade; the high grade lymphomas (are) still (treated with) a lot of traditional cytotoxic chemotherapy given the infusion center.

With follicular and some of the other slow-growing lymphomas, we have more utilization of these oral agents, (like tazmetostat). For example, FL PI3 kinase inhibitors, EZH2 inhibitor, lenalidomide.

Those are actually sometimes harder to get for patients than the IV stuff. It is much easier to get payers to pay for something where people have to come to the infusion center, but to get an (oral) drug that costs $2000 a dose can be more of a struggle.

There's some people who don't have enough prescription drug coverage to take care of that.

Most of the time, we'll figure it out. The manufacturer will have some kind of program, (or foundations like) Lymphoma Research Foundation, or Leukemia & Lymphoma Society, will have money. Once in a while, you do come across a situation where you have a copay, or a drug cost that is prohibitive, to using the thing you want to use.

OLN: How do you personally encourage your patients to enroll in clinical trials?

Dr Brem: I think it depends a lot on the trial and the patient.

For example, I have one study right now kind of looking if FL something it's kind of considered a standard versus standard plus something else.

(Studies like this are) easy to explain to patients where you say, "Hey, you're going to get the thing that we know works as a standard of care no matter what. You might also get this other thing, which may make work better, may have more side effects. We don't know, that's why we're doing the study."

Since in that particular situation you know at the very least they're getting something that's standard, those are often easy trials for patients to understand and those usually enrolled fairly well.

Then, you have the other patient who maybe doesn't have an FDA-approved option and then you're offering them something where we know what they're going to get. For example, a phase 2 study, but we don't know how efficacious it's going to be.

You're now asking them to sign up for something where we don't know if it's going to work. It might give them side effects, but again, this is why we do the clinical trials.

There’s different reasons to put patients on clinical trials. Patients can go on clinical trials at different points in their treatment experience. How I approach or how I explain it is very different depending on the specific situation the patient's in.