Brentuximab vedotin in R/R LBCL

On February 11, 2025, the U.S. Food and Drug Administration (FDA) approved the antibody–drug conjugate brentuximab vedotin in combination with lenalidomide + rituximab (BV+R2), for the treatment of adult patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after ≥2 lines of systemic therapy who are ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor (CAR) T-cell therapy.¹ This approval was based on positive results from the phase III ECHELON-3 trial (NCT04404283), which showed that BV+R2 improved outcomes vs placebo + R2 (Pbo+R2) in this patient population.^1,2

The primary mechanism of action of brentuximab vedotin is the targeted delivery of monomethyl auristatin E (MMAE) to CD30-expressing tumor cells to induce apoptosis.³ Studies have shown that response to brentuximab vedotin is not correlated with CD30 expression levels, suggesting that factors beyond CD30 targeting, such as bystander effects or immune modulation, may contribute to the antitumor activity.^3–5

Results from a post hoc analysis of the ECHELON-3 trial, presented during the 67th American Society of Hematology (ASH) Annual Meeting and Exposition 2025, December 6–9, 2025, Orlando, US, suggest that visible CD30 detection by immunohistochemistry (<1% vs no staining) is not required for response to BV+R2 in patients with R/R DLBCL.⁵

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