Third Line Therapies in R/R FL
An expert in follicular lymphoma highlights the therapies available for third-line relapsed/refractory treatment options.
Kristie L. Kahl: How does treatment choice after first relapse impact treatment options in later lines?
Connie Batlevi, MD, PhD: Very simply, we don’t commonly repeat treatments because there are so many different types of treatments, and repeated exposure can either increase your toxicity or the lymphomas can develop resistance to the prior treatments. We don’t ever say never, but that’s a general concept.
Kristie L. Kahl: What clinical end points are most meaningful to you?
Connie Batlevi, MD, PhD: The meaning changes depending on the patient. For example, if I have a [patient in their 60s] who is still working hard in their career, but their follicular lymphoma keeps coming back to interrupt their life, what’s meaningful to them is to have an effective form of treatment to get their disease under control. In contrast, if I have an octogenarian who has 0 tolerance for any treatment that can create symptoms, and can be quite fragile, the goal for this treatment is to have some disease control and some symptom control while maximizing how tolerable a treatment may be.
Kristie L. Kahl: What are the treatments that are available for the third-line setting for relapsed/refractory follicular lymphoma?
Connie Batlevi, MD, PhD: There are so many treatments available for third line and beyond. Mentally, I classify treatments into chemotherapy vs nonchemotherapy options first. Classically, any chemotherapy remains an option, though it’s not likely going to be the forefront of our resources. In the same chemotherapy concept, there are autologous stem cell transplants, which are high doses of chemotherapy. In terms of the nonchemotherapy options, they fall into different classes, like PI3 kinase inhibitors, EZH2 inhibitors, immune-based therapies like CAR T cells [chimeric antigen receptor T cells], and then also an allogeneic stem cell, which is essentially an immune replacement therapy to control follicular lymphoma.
Kristie L. Kahl: Are treatment goals for the third-line setting and beyond the same as the second-line setting?
Connie Batlevi, MD, PhD: No. This is also an individualized plan, and probably why taking care of follicular lymphoma patients can be so gratifying. By this time, you’ve understood that person’s life goals and what their short-term and long-term goals are, and depending on their disease course with the lymphoma and their life goals, the treatment recommendations can vary. As an example, I have a patient who recently retired and has been living with follicular lymphoma for over 15 years. He even was successfully treated for a second cancer, not related to the lymphoma. With the last relapse, he had localized disease that was in the radiation field, so we made radiation a part of his treatment. In another patient, he’s a farmer who lives far away from me. His disease keeps coming back, but it’s not transformed—we biopsied to prove that—and it’s also not very extensive, not very bulky, and it’s not impeding his function. He progressed after a couple of different treatments, including PI3 kinase inhibitors, and unless he was up for coming to Manhattan and spending some time getting his disease controlled at a major city or a major academic center, he didn’t have many choices. We sequenced him, and even though his lymphoma didn’t have an EZH2 mutation, we tried tazemetostat, and thus far he’s been doing great. From what I hear, that has given him limited adverse effects, if any, and he also doesn’t have to drive into the city to see me.
Kristie L. Kahl: When it comes to treatment for the third-line setting and beyond, how important is molecular testing?
Connie Batlevi, MD, PhD: I strongly believe in molecular testing for lymphomas in general. Particularly for follicular lymphoma, EZH2 inhibition is the first molecularly targeted treatment in all of lymphoma. Being able to interpret and have that additional information can help guide you. As I mentioned, I use tazemetostat on EZH2 wild-type patients, and it’s because we know that about 70% of follicular lymphoma have inherent genetic features that are regulated by epigenetics. Tazemetostat is a drug that regulates the epigenomics in a patient. The response rates are lower, but when they do respond, patients can respond for a good amount of time.
Transcript edited for clarity.
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