New and Emerging Therapies for Follicular Lymphoma, Including Treatment Challenges

By Blood Cancers Today Staff Writers - Last Updated: April 19, 2023

A roundtable discussion, moderated by Kami J. Maddocks, MD, of the James Cancer Hospital, Ohio State University Comprehensive Cancer Center, focused on treatment options for diffuse large B-cell lymphoma and follicular lymphoma (FL), including novel emerging therapies and treatment sequencing considerations. Dr. Maddocks was joined by a panel that included Pierluigi Porcu, MD; Pamela Blair Allen, MD, MSc; and Jonathan W. Friedberg, MD.

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In the next segment, the panel discusses novel treatment options for FL, including bispecifics, CAR-Ts, monoclonal antibodies, and more.

*Editor’s note: After the live taping of this roundtable, the FDA approved mosunetuzumab on December 22, 2022, for the treatment of relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

Dr. Maddocks: Let’s kind of have the same discussion on follicular lymphoma. What are some of your thoughts on the bispecific antibodies that the data we’ve seen in follicular lymphoma?

Dr. Friedberg: I think there, we’re optimistic that we’re going to see an approval of mosunetuzumab within the next few weeks of this recording. At least the FDA is considering it before the end of the calendar year.* So I think that implies that there’s a reasonable efficacy base. And the question then is when do you use it? And of course this is a disease, we talked about just earlier, it’s so heterogeneous, but I think having that as an option for patients who maybe have progressed after chemoimmunotherapy and lenalidomide-based therapy, whether it’s used before or after CAR T-cell therapy, and we’re still learning about the optimal use of CAR T-cell therapy in follicular lymphoma, but I think this will be another important tool that will be looked at earlier and earlier in subsets of patients with follicular lymphoma as well.

*Editor’s note: After the live taping of this roundtable, the FDA approved mosunetuzumab on December 22, 2022, for the treatment of relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

Dr. Maddocks: I think maybe even more exciting in follicular just from the standpoint of in large-cell, you’re willing to tolerate a little more toxicity, but it’s nice to have these when you’re looking at the option of this in CAR-T in follicular lymphoma where maybe your patients have more options, live longer…

Dr. Friedberg: And mosunetuzumab, at present, is infusional, but the company is working on a subcutaneous formulation, and it’s expected that will be what’s used. And with that approach, at least we’re told that the risk of CRS or hospitalization is very low, and that may be striking that balance that you were asking for.

Dr. Maddocks: What about some of the CAR products? So again, the CD19 CARs are effective in follicular. I think it’s a challenge to decide what are the right patients for those products right now. I don’t know if you guys want to maybe comment on where you see it, the current product approval use in any products that you see as exciting in this area.

Dr. Friedberg: I will say I’m a bit concerned about the durability of CAR-T in follicular as compared to diffuse large B-cell lymphoma. We don’t have the length of follow-up and the studies are smaller, but if you look at the curves, they don’t appear to be quite flattening like they did in large-cell lymphoma. And that could be disappointing because I think we’d like to think that it’s definitive treatment if we use it. I think right now we think about it at our institution and patients with early progression who have aggressive clinical courses or the multiply relapsed setting.

Dr. Porcu: Young, maybe, with a high tumor burden, younger patient, those are tough with follicular lymphoma.

Dr. Allen: Agree. Patients that have relapsed especially if they’ve relapsed within a year of chemotherapy are certainly a high-risk cohort that we certainly worry about, but I think the other benefit of CAR-T is that it’s not a long duration of therapy. It’s like one time. So for where I am, a lot of times patients travel quite far to come see me. So it’s nice to be able to give something that you can give in the hospital and then let them go back to the community.

Dr. Maddocks: I think in the multiple relapse young patients and in the POD24, it’s a nice option, but I agree, I think we’re not seeing that durability necessarily or it looks like we might not be that we see in some of the patients with large-cell.

Dr. Friedberg: I think as you were implying, the toxicity though appears to be less than in large-cell lymphoma. So whether that’s an indicator of immune fitness and you need a little bit more activation to get these CARs to work, it’s not clear to me, but at least it’s been our experience that most of the patients with follicular lymphoma almost fly through the treatment.

Dr. Maddocks: What about some of the other therapies? Anything from monoclonals, antibody-drug conjugates, or even oral therapies here that you think is exciting?

Dr. Porcu: The loncastuximab data I think are looking pretty good both in terms of efficacy as well as safety. I think we still need to see the durability of some of those responses. I tend to think of antibody-drug conjugates as a variant of chemotherapy to some degree more than just really sort of immunotherapy. So in terms of resistance to therapy failure after chemotherapy, but the data are promising. So I think that that’s another drug to keep an eye on.

Dr. Allen: You had mentioned earlier tazemetostat. It’s a very tolerable drug, so when we’re talking about ability to be able to tolerate side effects that’s another therapy that is reasonable.

Dr. Friedberg: So my provocative comment number two is mentioning the category of drugs called PI3K inhibitors, which I think somewhat sadly we know across many different drugs in that class had significant activity in follicular lymphoma. And I’m certain that all of us at the table have individual patients we can think of who really benefited from that drug class. And largely because of toxicities and other diseases that were observed, that drug class has virtually disappeared with the exception of copanlisib, but at this meeting, zandelisib and some other new schedules and strategies of PI3K inhibitors appear to be still under development and to some degree a resurrection of that, in a careful, thoughtful way I think would serve the field well.

Dr. Maddocks: I completely agree. I think that was unfortunate because they do work well in some patients, and some do tolerate them well and it’s nice to have those options.

Continue on to watch the next roundtable segment.

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