New Developments in First- and Second-Line Treatments for Patients With Aggressive DLBCL

John Leonard, MD, Weill Cornell Medicine, NewYork-Presbyterian Hospital, discusses recent therapeutic developments for aggressive diffuse large B-cell lymphoma (DLBCL) in the first- and second-line treatment settings, highlighting recent data around pelotuzumab vedotin and CAR-T therapies in this space.

Dr Leonard presented on this topic at the 2022 Great Debates and Updates in Hematologic Malignancies meeting in New York, NY.

Transcript:

I'm John Leonard. I'm a professor of medicine and senior associate dean at Weill Cornell Medicine and New York Presbyterian Hospital here in New York. The focus of my presentation at the meeting was on new developments in the initial therapy and in the second line therapy of diffuse large B-cell lymphoma.

After many years, R-CHOP has been the standard treatment for the vast majority of patients with diffuse large B-cell lymphoma. And in recent months, we've had some important new studies in this area. The first is the POLARIX study, which focused on polatuzumab vedotin, an antibody drug conjugate swapping in that drug for vincristine in the R-CHOP regimen. And that is a regimen that was explored in a randomized trial compared to R-CHOP in patients with International Prognostic Index risk group 2 through 5.

The net of that study was positive, essentially suggesting that this may be a new standard of care for some patients with previously untreated diffuse large B-cell lymphoma. Despite the fact that there's no overall survival benefit, this efficacy benefit may inform our practice and change the standard of care for at least a subset of these patients.

The other focus of my presentation was on new data in the relapse setting. We have been using CD19-directed CAR T-cell therapy as third line and later therapy for patients with recurrent diffuse large B-cell lymphoma. We've had several recent studies presented that compared second line therapy with the standard chemotherapy followed by autologous stem cell transplant versus using CAR T-cell second line.

And 2 of these 3 studies were positive studies, suggesting a clear event-free survival benefit and the possibility of an overall survival benefit as well. One study was negative, which had some different features to it. I think these data have really also now informed the second line therapy of diffuse large B-cell lymphoma, particularly for patients that have progressed within a year of their initial therapy.

To summarize and conclude, after years of using the same regimens we now in the last several months have 2 new approaches: one, using a new drug as part of upfront therapy, one using CAR T-cells as second line therapy. I think [these new approaches] are dramatically going to improve outcomes for subsets of patients with diffuse large B-cell lymphoma, and are very much practice-changing for oncologists who see lymphoma patients.