Newly Approved Triplet Regimen Boosts Survival in R/R LBCL: Craig Portell, MD

The triplet regimen of brentuximab vedotin (Adcetris; Seagen), lenalidomide, and a rituximab product was approved by the FDA in February for treatment of relapsed/refractory large B-cell lymphoma (LBCL), encompassing diffuse LBCL (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, and high-grade BCL. This approval was supported by data from the ongoing phase 3 ECHELON-3 trial (NCT04404283), in which patients were randomized 1:1 to receive brentuximab vedotin/lenalidomide/rituximab or placebo/lenalidomide/rituximab. An 18-month overall survival and a 47% reduced risk of death were seen among patients not eligible to undergo autologous hematopoietic stem cell transplantation (auto-HSCT) or to receive chimeric antigen receptor (CAR) T-cell therapy.

Discussing the approval with The American Journal of Managed Care^®, principal investigator Craig A. Portell, MD, UVA Health, explains why this approval is so significant—these patients “are often in a difficult situation,” he says—and how it expands treatment options for this patient population. Portell is also an associate professor of medicine at the University of Virginia in Charlottesville, where his work focuses on lymphoma and chronic lymphocytic leukemia clinical trials and clinical care for patients.

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

Transcript

What were your primary and secondary goals for ECHELON-3, and did any findings surprise you?

The primary goals were really to see if the combination was any better than lenalidomide and rituximab alone. As far as efficacy, I believe it’s measured as survival. I think we were kind of surprised that the addition of brentuximab vedotin to lenalidomide and rituximab did show an overall survival advantage, and why that is, we're not 100% sure yet. We hope that there will be some translational work to determine some mechanisms of action here, why one treatment kept people alive a little bit longer than the other treatment did.

Is there an unmet therapeutic need for these patients that you are hoping to address?

Patients with relapsed diffuse large B-cell lymphoma are often in a difficult situation, although with newer techniques now, there are many treatment options available for them, from bispecific antibodies to other combination chemotherapy. This triplet combination—the brentuximab vedotin, lenalidomide, and rituximab—is a very reasonable option for some patients, particularly those that want to spend less time in an infusion center or have contraindications to things like bispecific antibodies or more complex chemotherapy regimens. Yes, there are unmet needs in the relapsed lymphoma/large cell lymphoma space, mostly because many of our patients will ultimately have short remissions that can then be salvaged with other therapies, so this gives us another therapeutic option.

How does this approval change the treatment landscape for patients ineligible for auto-HSCT or CAR T?

I think it shows us that, in the past, we would have used lenalidomide and rituximab alone, but now the addition of brentuximab vedotin is clearly more helpful than the doublet. It does give us another option for those patients who have either failed auto transplant or CAR or who are not eligible for those treatment options. We don't have a lot of known treatment options available for patients in that space.