Future Directions and Unmet Needs for Treatment of DLBCL


Andre Goy, MD, MS: How do we approach the clinical trial? I think it’s a great way to conclude this. First of all, we need everyone to participate and refer patients for clinical trial. This is the way we move the needle, and this is the way R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] was designed. This is the way that progress has always been made. Wrapping up in conclusion, a few minutes per person, Peter, briefly, what is your most important take-home message in large cell lymphoma and a few words on trials?

Peter Martin, MD: My take-home message regarding clinical trials is one that’s mostly relevant to us and that we’ve seen over and over, and we’ll see again, that patients who participate in clinical trials frequently have superior outcomes. There are a variety of reasons for that, but the clinical trial itself may be part of that. There are some groups who historically have not been able to participate in clinical trials, underserved populations, rural populations. As hard as we can try to bring them in to our centers, that’s not always practical, and that has not worked. I think that we have to make more of an effort as a research community to bring clinical trials to populations that historically have not had access to them. I think that all of us actually have looked recently at a funding opportunity from the Leukemia & Lymphoma Society, which rightfully perceives this as a weakness. So, I think that it’s an important point.

Andre Goy, MD, MS: The disparity issue is a very big issue. There was a presentation at ASCO [the American Society of Clinical Oncology], I believe, and there’s a presentation at ASH [the American Society of Hematology] looking at the African-American population in the southern states of the United States that was about 1000 patients, 300 African-American. The outcome was dramatically worse, and it was not from the time to treatment. It was from comorbidities, and dose reduction, and so forth. Quickly wrapping up our conclusion, Grzeg, comment on lymphoma, large cell lymphoma, and provide any advice you may have to our audience.

Grzegorz S. Nowakowski, MD: I would echo what Peter said that clinical trial is the standard of care. We have so many new agents and developments in this field that we have to make every effort to enroll patients on clinical trials. The other conclusion is that the field is changing extremely rapidly. We are where we are today, but I think in the next several years, we’ll see major changes. CAR [chimeric antigen receptor] T-cell therapy may be moving more to upfront therapy or at least the second-line therapy. Some of those antibodies, immunoconjugates will really revolutionize what we do.

Andre Goy, MD, MS: Kami?

Kami Maddocks, MD: I would echo what Peter and Grzeg said. I would say clinical trials are always the right answer. Our job should be to better include patients, have better inclusion and exclusion criteria, so they’re easier for patients to get on and we’re not excluding what patients we’re defining as real-world populations. I think we’ve made significant progress in the relapsed setting in the last couple of years with the CAR T, the POLA [polatuzumab vedotin]-BR [bendamustine, rituximab] was the first approval in that setting. Hopefully things like the tafasitamab and LEN [lenalidomide] will improve that even further. But I think that post-CAR T is going to be a big population and an unmet need, especially as we move it forward, and we do have to find good options for those patients.

Andre Goy, MD, MS: We do. As part of a larger topic on the clinical trials point is that drug development we need to accelerate, obviously. Then when we do change, we do it on regulatory basis as well because it’s not moving fast enough. We need to get a conditional approval very early on, based on a signal that it is showing promising activity in phase II, and monitor very carefully the level of toxicity and efficacy in real-world data, and confirm or modify the label based on what we see in the real world. Otherwise it’s not going to move fast enough. Nathan, final thoughts on lymphoma?

Nathan H. Fowler, MD: The good news is large cell lymphoma outcomes are getting better. The bad news is that we are incredibly inefficient in the way we conduct clinical research across the world. Right now, there’s a major gap in the biological understanding of these diseases and what we do in clinical practice. That was highlighted in the beginning of this talk when we talked about how we have all these subsets, we understand some of the genomic profiles. But we have no way to stratify patients in a different therapy based upon this knowledge. What they’re doing at the laboratory has yet to translate really into what we do in the clinic. I think some of that has to do with the lack of mechanistic and correlative studies that occur in our clinical trials. So again, if we continue to enroll….

Andre Goy, MD, MS: To validate what….

Nathan H. Fowler, MD: Yes. We continue to put thousands of patients on trials, and if you look at the percentage of trials that actually have correlates built in to help understand how these drugs work and who they work in, it’s extremely small.

Andre Goy, MD, MS: Often it’s an issue because it has to be made optional, or it is an issue because it slows down the enrollment.

Nathan H. Fowler, MD: We have to push for these types of studies and clinical trials.

Andre Goy, MD, MS: Liquid biopsies might help this.

Nathan H. Fowler, MD: I think it is getting easier. As you mentioned, there is ctDNA [circulating tumor DNA], and there are a lot of ways we can potentially look at the peripheral blood instead of requiring repeat biopsies. But again, I think right now we’re really seeing a gap between what we understand in the lab and how we’re practicing in the clinic. The only way we’re going to change that is to integrate some of these studies in the clinical trials.

Andre Goy, MD, MS: Dr Chavez?

Julio Chavez, MD: Well, I think there are several options for DLBCL [diffuse large B-cell lymphoma] that are in the pipeline. But I would recommend moving the early referral, especially for the cases that we know are going to be the bad actors, like…lymphomas, always recommend referral to an academic center to make sure that we recommend the right treatment. Also recommend referral for the early relapse, and in general, the relapsed patient because there could be options for them for the future.

Andre Goy, MD, MS: I think the future is great. I think we are very fortunate to be oncologists at this time. This is a challenge because we have so much innovation going. We didn’t even talk about data analytics. We just talked about clinical trial and drug development. It is important that we partner all together, we defragment healthcare as much as we can because it’s a real problem. We see patients, you give them a treatment, and then we don’t see them the next time around, and it makes it very difficult. There is a huge effort in sharing data and sharing information, and it’s a real challenge.

The regulatory effort needs to be done for the drug development, to change the way and to allow people to get access to tissue, samples, and liquid biopsies repeatedly because this is a real challenge. If you don’t do this systematically, it never happens unless you have a champion locally. Mayo Clinic may be different. But this is a real challenge. The vast majority of patients are treated in the community, so we hope that this program was very helpful to you and shed some light on the bright future of large cell lymphoma. We thank you on behalf of our panel. We hope you found this Peer Exchange discussion very interesting and informative. We wish you good luck in caring for your patients. Thank you.

Transcript Edited for Clarity

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