Challenges Remain for Improving Non-Hodgkin Lymphoma Treatments

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, 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.

In the next segment, the panel discusses barriers to improving treatment options for patients with DLBCL and follicular lymphoma, including clinical trial participation challenges.

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Dr. Maddocks: So when we’re looking at trying to improve outcomes in some of these populations like the relapsed/refractory or high-risk frontline, what do you guys see as some of the barriers to getting improved treatments or studying improved treatments?

Dr. Allen: I think part of it is getting them on trial in the first place. We certainly have had those studies that show the time to treatment as a major predictor of outcomes, meaning patients that need to be admitted for emergent therapy are going to do much worse, and then that is the patient population where we really should be targeting in clinical trials, but it’s really tough to get them on clinical trials if they’re being emergently admitted to the hospital to start therapy. So I think incorporating changes in trial design, which is starting to happen to allow a cycle of chemotherapy before the rest of the study-initiated treatment, I think is really helpful for those patients.

Dr. Porcu: The elderly and frail population clearly remains a tough population to find proper therapies for. And so I’d be very curious to see some of the data coming up with less intensive therapies for those patients, perhaps immunotherapy combinations in the frontline.

Dr. Friedberg: I think that’s an important point when you think about barriers to clinical trial accrual, the median age of this disease is between 65 and 70, and the median age of the patients who relapse is likely higher than that because age is an indicator for higher-risk disease. So it’s likely that almost the majority of patients with relapsed disease are not going to ever be candidates for the very aggressive approaches.

And with clinical trial criteria that include creatinine clearance cutoffs and other things, you end up excluding large numbers of patients, and I think that may be the biggest barrier. And a push to try to have trials that are specifically targeting that population has started. We have one in the NCTN that is open for patients over the age of 75 that’s designed specifically for those patients, and I’m optimistic that with those types of initiatives we’ll be able to learn quicker on ways to improve outcomes.

Dr. Maddocks: Let’s pivot to follicular and some of the same discussion in follicular. What do you see as some of the major unmet needs in patients with follicular lymphoma?

Dr. Allen: I guess it’s part of diffuse large B-cell, but patients that develop large cell transformation, I feel like that can be still a kind of complicated area to treat and knowing what’s the appropriate therapy and when, especially depending on what they had previously for their follicular lymphoma.

Dr. Friedberg: I guess I’ll be provocative and say that I’d like to see us try to cure follicular lymphoma, and I might submit that a subset of patients we’re probably curing already. If you look at 10-year follow-up of people treated with chemo-immunotherapy, almost 40% of those patients remain progression-free and haven’t needed any treatment. And there are few situations in medicine where you go 10 years and you don’t at least mention the word cure, appreciating the long natural history of this disease. I think there are opportunities both with low tumor burden and higher tumor burden presentations for us to think as carefully as we can about strategies that will be limited-duration treatments with a goal to cure the disease.

Dr. Maddocks: So I’ll be a little provocative back. Do you think that cure will come in some of the newer immunotherapy-type treatments or what are you what do you think’s most promising?

Dr. Friedberg: I think absolutely. If you take low tumor burden follicular lymphoma where we do have the RESORT trial that has presented long-term follow-up, there’s a proportion of patients that with four doses of rituximab have disease that stays away for a very long period of time. And that suggests to me that for that common presentation of follicular lymphoma, an immune-based approach may be the beginning of a way to cure this disease. And this goes back to even the studies of vaccines and other approaches in the ’80s and ’90s. So I think bispecific antibodies, balancing tolerability with efficacy, represent great promise in that direction. I agree with you.

Dr. Maddocks: What about the barriers? Because follicular lymphoma can have such a heterogeneous patient population, I think that can be challenging. What do you see as some of the barriers to addressing the unmet needs in follicular lymphoma?

Dr. Friedberg: I’ll say that we don’t have any molecular signature or predictors at diagnosis on who’s going to do well and who isn’t. We’ve looked at that, and we have a little bit of a hint maybe with the FLIPI or clinical indices, there’s some genomic panels that have not become standard of care, but it’s frustrating to meet a patient and say that they’re likely to do very well, but there’s a chance that they won’t, and the only way to know which category they’re in is to sit and watch.

Dr. Porcu: Especially for frontline patients with follicular lymphoma, most of those patients are treated really in the community. So I think it’s difficult to get them on large clinical trials trying to change the landscape on the frontline setting.

Dr. Maddocks: I think that can be a challenge in relapsed/refractory disease too, just because they have options, it’s great that they have so many options but then they’re treated in the community and it’s harder sometimes to get these patients on trials because they have options outside of that.

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Continue on to watch the next roundtable segment.