Dr Ann LaCasce: T-Cell Engagers Have Improved DLBCL Outcomes, but Questions on Optimal Use Remain

With T-cell engagers such as chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies moving into earlier lines of therapy, answering questions about which patients will benefit most from these therapies is a key next step, said Ann LaCasce, MD, MMSc, director of the Dana-Farber/Mass General Brigham fellowship in hematology/oncology and chair of the Lymphoma Research Foundation’s Scientific Advisory Board.

Transcript

T-cell engager therapies such as CAR T cells and bispecific antibodies have become preferred regimens in guidelines for certain relapsed/refractory lymphomas. How do you see this space evolving moving forward?

I think these have been really important additions to our therapeutic options. In diffuse large B-cell lymphoma 7 or 8 years ago, when patients relapsed quickly after initial therapy or were primary refractory, we had very little we could do. And now with the availability and the approvals of second-line CAR T-cell treatment, this has really been a huge improvement.

I think the question now is, how do we predict who's going to be a long-term remitter or cured with CAR T-cell therapy? And what are those mechanisms of resistance? And how can we better understand why the patients who fail CAR T, why do they fail? Do we need CARs that are different that engage more than 1 receptor, [like] combined CD19/CD20? Or do we need different costimulatory molecules? Or should we be adding bispecifics to CAR T?

There's all kinds of directions that this is going in, but I think the key is going to be, in diffuse large B-cell lymphoma, to really understand the biology of these diseases and try to predict who's going to benefit and who's not. And can we use some of these new techniques like MRD [minimal residual disease] to predict early that patients are destined to relapse? Because we know that all of these treatments really are most effective when patients have asymptomatic, relatively low-burden disease. So, I think integrating the science is going to be key to moving this field forward.