ASH 2025 | Smart Stop: lenalidomide, tafasitamab, rituximab, & acalabrutinib ± chemo in newly diagnosed DLBCL

At the 2025 meeting, we presented the primary analysis of the Smart Stop trial. This is a trial that we did at MD Anderson as a follow-on to a study we previously did called the Smart Start trial. Both of these trials are evaluating the potential of novel combinations in patients with newly diagnosed diffuse large B-cell lymphoma. For nearly 50 years, CHOP has been the backbone of chemotherapy, and all new targeted agents have been added to CHOP. But we’ve explored the possibility of adding a targeted agent to a targeted agent. And in the Smart Stop clinical trial, we did a four-drug combination, lenalidomide, tafasitamab, rituximab, and acalabrutinib – we call it LTRA – and patients get four cycles of that treatment. If they have a CR, they would get less or no chemotherapy for newly diagnosed large cell lymphoma. 

In the analysis we presented at this meeting, we had a 57% complete response rate and excellent outcomes. More than 90% overall survival, 98% overall survival at two years, 86% progression-free survival. But what’s really important is that the patients who received less or no chemotherapy did very well. And the few patients who had a progression of their disease after having no chemo were able to get a CR to go ahead and get chemo. The patients who had less than a CR to the lead-in got a CR to chemo, which basically means we can now conclude that the targeted therapy upfront, the Smart clinical trials, do not compromise curative intent and are a vehicle for us to explore ways to improve outcomes in large B-cell lymphoma.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.