Future Research Priorities for Non-Hodgkin Lymphomas: Craig A. Portell, MD

In February, the FDA approved a novel triplet combination for relapsed/refractory large B-cell lymphoma, a type of non-Hodgkin lymphoma, based on data from the ongoing phase 3 ECHELON-3 trial (NCT04404283), in which patients have been randomized 1:1 to receive brentuximab vedotin (Adcetris; Seagen)/lenalidomide/rituximab or placebo/lenalidomide/rituximab. Principal investigator Craig A. Portell, associate professor of medicine at the University of Virginia in Charlottesville and of UVA Health, previously spoke to this approval’s significance in expanding the treatment pool for these patients.

Here Portell looks to the future of research in this space for these patients and addresses survival questions that persist, even as he emphasizes that follow-up is “always a positive for our field.”

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

With ECHELON-3 expected to complete in 2027, what key questions remain about the long-term impact of this triplet regimen?

The optimal dose has kind of already been worked out in prior studies, and this was a randomized study. Not a lot of patients are still in treatment. Unfortunately, this space is a space where patients have, again, relapsing/remitting course. I think some of the extended follow-up will help with understanding the long-term survival and managing the short-term survival, like does that survival curve still maintain, or are there other cofactors that may change it? I think that there's not terribly much that's going to be gained by the continued follow-up, just because there's not that many patients that are still left on treatment. But continued follow-up is always a positive for our field.

What should be future research priorities for treating this hematologic malignancy?

I think there's a few. We've considered large B-cell lymphoma, diffuse large B-cell lymphoma, and all of its different caveats. [In] clinical studies, at least, we consider it 1 disease, but we know it's probably not. We know it's probably a basket term for multiple different aggressive B-cell lymphomas, and it would be nice to know, with additional testing, additional work as far as cell of origin and the subtype of diffuse large B-cell lymphoma, which treatments that we have available to patients could be more effective than others for various different biological subtypes. I think that would be one place where research would be really helpful in this disease, because we do have many different treatment options available for relapsed diffuse large B-cell lymphoma, and oftentimes it's not biologically driven but somewhat clinically driven and based on prior treatments.

But it would be nice to have a better understanding of what the biologic rationale for various different treatments are. And then, because we have many different agents and most of them are single agents, I think it would be nice to see how some of these drugs work together. Can we combine some drugs together and get better efficacy, maybe with some increased toxicity, like we saw with ECHELON-3, but maybe that is offset by the improved efficacy that we would see with combination.

I think those are the 2 major things I would think for future research. One, can we combine these drugs together and get better efficacy, and (2) can we use biology to predict better treatments for our patients that may be more effective in different subgroups?