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FDA grants approval to brentuximab vedotin with lenalidomide plus rituximab for relapsed/refractory LBCL

On February 11, 2025, the U.S. Food and Drug Administration (FDA) granted approval to brentuximab vedotin (BV) combined with lenalidomide plus rituximab (R2) for adult patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) who have received at least two prior lines of systemic therapy and are ineligible for autologous stem cell transplantation (autoSCT) or CAR T-cell therapy. This includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL progressing from indolent lymphoma, and high-grade B-cell lymphoma (HGBL).1

Brentuximab vedotin, an antibody-drug conjugate targeting CD30, has previously shown efficacy in advanced-stage classical Hodgkin lymphoma (HL) and anaplastic large cell lymphoma or other CD30‐expressing peripheral T‐cell lymphomas (PTCL). The agent was approved for these indications in 2018 based on data from the ECHELON-1 (NCT01712490) and ECHELON-2 (NCT01777152) clinical trials.2,3

The approval of the BV+R2 combination therapy for R/R LBCL is supported by findings from the ECHELON-3 study (NCT04404283), a randomized, double-blind, placebo-controlled Phase III trial.1 This trial randomized 230 patients (median age 71 yrs; range 21-89) with R/R LBCL in a 1:1 fashion to receive BV+R2 or placebo+R2 until disease progression or unacceptable toxicity.4

The primary endpoint of the study was overall survival (OS) in the intent-to-treat population. Secondary endpoints included progression-free survival (PFS) and overall response rate (ORR) assessed using the 2014 Lugano Criteria. At a median follow-up of 16.4 months, a statistically significant improvement in OS was observed in patients treated with BV+R2, with a median OS of 13.8 months (95% CI: 10.3-18.8) in the BV+R2 arm compared with 8.5 months (95% CI: 5.4-11.7) in the placebo arm (hazard ratio 0.63; 95% CI: 0.45-0.89; p=0.0085). Both PFS and ORR also improved with the addition of BV to R2. Median PFS for BV+R2 was 4.2 months (95% CI: 2.9-7.1) versus 2.6 months (95% CI: 1.4-3.1) with placebo+R2 (HR 0.53; 95% CI: 0.38-0.73; p <0.0001), and the ORR was 64.3% (95% CI: 54.7-73.1) and 41.5% (95% CI: 32.5-51.0), respectively.1

Regarding safety, common adverse events occurring in ≥20% of patients receiving BV+R2 were fatigue, diarrhea, peripheral neuropathy, rash, pneumonia, and COVID-19 infection. Decreased neutrophils, lymphocytes, platelets, and hemoglobin were observed in over 10% of patients. In 27% of patients, an onset or worsening of peripheral neuropathy was reported, leading to BV dose reduction in 6% of cases and discontinuation of the agent in 4.5%.1

The approval of this combination approach provides a novel therapeutic option for a heavily pretreated, transplant-ineligible patient population with limited alternative treatment options.

References

  1. U.S. Food and Drug Administration. FDA approves brentuximab vedotin with lenalidomide and rituximab for relapsed or refractory large B-cell lymphoma. Available here. (Last accessed 13/02/2025).
  2. U.S. Food and Drug Administration. Brentuximab Vedotin. Available here. (Last accessed 13/02/2025).
  3. U.S. Food and Drug Administration. FDA approves brentuximab vedotin for previously untreated sALCL and CD30-expressing PTCL. Available here. (Last accessed 13/02/2025).
  4. Kim J, Hahn U, Kim W, et al. Brentuximab vedotin in combination with lenalidomide and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma: Results from the phase 3 ECHELON-3 study. JCO. 2024 Jun; 42,LBA7005.

Written by Natalie Markova

Edited by Anya Dragojlovic Kerkache