Brentuximab Vedotin Plus Lenalidomide and Rituximab Receives FDA Approval for Adults With LBCL

Author(s):

Gillian McGovern, Associate Editor

Key Takeaways

Brentuximab vedotin, lenalidomide, and rituximab combination is approved for relapsed/refractory LBCL patients ineligible for auto-HSCT or CAR T-cell therapy.
ECHELON-3 trial showed improved overall survival, progression-free survival, and objective response rate with the combination therapy.
Common adverse events included fatigue, diarrhea, peripheral neuropathy, with higher rates of neutropenia and anemia in the treatment group.

The approval follows the ECHELON-3 study, which enrolled adults with relapsed or refractory large B-cell lymphoma.

The FDA approved brentuximab vedotin (Adcetris; Seagen Inc) when used in combination with lenalidomide (Revlimid; Bristol Myers Squibb) and a rituximab (Rituxan, Mabthera; Genentech, Roche) product to treat adult patients with relapsed or refractory large B-cell lymphoma (LBCL)—diffuse LBCL (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma—after 2 or more lines of systemic therapy. Additionally, this indication is for patients who are ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or CAR T-cell therapy.¹

Image credit: monticellllo | stock.adobe.com

Brentuximab vedotin is a prescription medicine that is directed against the CD30 protein. It is currently used to treat adult patients with different lymphomas following certain treatments, either on its own or as a monotherapy, and to treat children 2 years and older with previously untreated high-risk classical Hodgkin lymphoma in combination with chemotherapy.^1,2

About the Trial

Trial Name: Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL (ECHELON-3)

ClinicalTrials.gov ID: NCT04404283

Sponsor: Seagen Inc

Completion Date (Estimated): April 30, 2027

The approval is based on the randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial, ECHELON-3 (NCT04404283).³ For this study, a total of 230 adult patients with relapsed or refractory LBCL who were ineligible to receive an auto-HSCT or CAR T-cell therapy were enrolled. Patients had a median age of about 71 years (range: 29-89 years); the majority (56.5%) were male. Additionally, the median prior lines of therapy were 3 (range: 2-8), and approximately 20% had prior CAR T-cell therapy. The primary study outcome measures were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).^1,3,4 Additionally, the investigators also assessed complete response rate, duration of response, and frequency of adverse events (AEs).³

Patients were randomly assigned to receive either brentuximab vedotin plus lenalidomide and rituximab (n = 112) or placebo plus lenalidomide and rituximab (n = 118) until disease progression or unacceptable toxicity.^3,4 Both brentuximab vedotin and placebo were administered intravenously (IV) every 3 weeks. For both groups, rituximab (375 mg/m²) was administered via an IV infusion on day 1 of the first cycle—with subcutaneous administrations allowed every 3 weeks starting on day 1 of cycle 2 through the end of treatment—and lenalidomide (20 mg) was administered orally.³

At a median follow-up of 16.4 months (range: 0.1-31.5 months), the median OS was about 13.8 months (95% CI: 10.3-18.8) for those treated with brentuximab vedotin compared with 8.5 months (95% CI: 5.4-11.7) for placebo (HR 0.629; 95% CI: 0.445-0.891; P = .0085). Additionally, the median PFS was favorable for brentuximab vedotin (4.2 months; 95% CI: 2.9-7.1) compared with placebo (2.6 months, 95% CI: 1.4-3.1; HR .527; 95% CI: 0.380-0.729; P < .0001). ORR was approximately 64.3% (95% CI: 54.7-73.1) and 41.5% (95% CI: 32.5-51.0; P = .0006), respectively.^1,4

The most common AEs, excluding laboratory abnormalities in the investigational cohort, consisted of fatigue, diarrhea, peripheral neuropathy, rash, pneumonia, and COVID-19 infection.¹ In the study, grade 3 or higher treatment-emergent AEs were reported in the brentuximab vedotin and placebo groups and included the following: neutropenia (46% vs 32%), anemia (29% vs 27%), and diarrhea (31% vs 23%). Additionally, rates of all-grade peripheral neuropathy for brentuximab vedotin compared with placebo were 31% and 24%, and 6% and 2% for grade 3.⁴

REFERENCES

1. US Food & Drug Administration. FDA approves brentuximab vedotin with lenalidomide and rituximab for relapsed or refractory large B-cell lymphoma. News release. February 11, 2025. Accessed February 12, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brentuximab-vedotin-lenalidomide-and-rituximab-relapsed-or-refractory-large-b-cell?utm_medium=email&utm_source=govdelivery

2. Discover ADCETRIS® (Brentuximab Vedotin). ADCETRIS. Accessed February 12, 2025. https://www.adcetris.com/

3. Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL (ECHELON-3). ClinicalTrials.gov identifier: NCT04404283. Updated November 13, 2024. Accessed February 12, 2025. https://clinicaltrials.gov/study/NCT04404283

4. Kim JA, Hahn U, Kim W-S, 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;42(Number 17 suppl):LBA7005-LBA7005. doi:10.1200/JCO.2024.42.17_suppl.LBA7005