Peter Riedell, MD, on DLBCL: Expert Commentary on Data From the ECHELON-3 Study

ECHELON-3 was a Phase 3 double-blind placebo-controlled trial in patients with diffuse large B-cell lymphoma that had relapsed or refractory disease to prior therapy. In this study, they particularly enrolled those patients that were either ineligible for or had received prior treatment with both CAR-T cell therapy or hematopoietic stem cell transplant. In this trial, investigators evaluated a combination of lenalidomide and rituximab with either brentuximab vedotin or placebo. It was a median of three prior therapies, and in general the patients were heavily pre-treated, including approximately half of patients having primary refractory disease, 30% of patients with prior CAR-T cell exposure, and approximately 15% of patients had prior bispecific antibody exposure. We see with the combination of brentuximab vedotin, lenalidomide and rituximab, that this is a very active regimen, and we're seeing high complete response rates along with encouraging durability at this point. These improved responses were encouragingly seen in both CD30-positive and CD30-negative patients, and this translated into an improvement in progression-free along with overall survival. And importantly, we saw some improvements in really key subsets of patients with high-risk features such as those with high IPI, those patients with prior CAR-T exposure, along with those patients with nongerminal center cell of origin, and this regimen though was not without its own toxicity, and we saw higher incidence of Grade 3 or greater adverse events in the [inaudible 00:01:40] and rituximab arm compared to lenalidomide-rituximab alone, particularly those manifested as hematologic toxicity, along with increased risk of peripheral neuropathy. In general this was an active regimen, and is particularly encouraging for those patients that may not be either eligible for, or have previously received, therapy with things like bispecific antibodies, CAR-T or hematopoietic stem cell transplant. This is currently an interim analysis, and we will need longer follow-up in order to have a better understanding of long-term outcomes, particularly in terms of both safety and efficacy.