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.

• DOI: 10.1200/jco.2024.42.17_suppl.lba7005
• Publication Date: 2024-06-05T13:28:57Z
• Authors: Jeong A Kim; Uwe Hahn; Won-Seog Kim; Isabelle Fleury; Kamel Laribi; Juan Miguel Bergu...; Krimo Bouabdallah; Nick Forward; Fontanet Bijou; David MacDonald; Craig Anthony Por...; Hervé Ghesquieres; Grzegorz S. Nowak...; Christopher A. Ya...; Evelyn Rustia; Michelle Fanale; Fei Jie; Nancy L. Bartlett
• Keywords: Brentuximab vedotin; Refractory (planetary science); Clinical endpoint; Interim analysis

LBA7005 Background: Despite recent advances, there remains a need for novel therapies pts with R/R DLBCL. BV, an anti-CD30 antibody-drug conjugate, has shown efficacy and safety when combined lenalidomide (len) rituximab (R) in heavily pretreated populations (Bartlett 2022; Ward 2022). The double-blind, global phase 3 ECHELON-3 study (NCT04404283) compared BV R+len (R2) vs R2 DLBCL who are ineligible HSCT or CAR T-cell therapy. Here, we present results from the interim analysis (IA) overall survival (OS). Methods: Pts received BV+R2 placebo+R2 (randomized 1:1). (1.2 mg/kg) placebo q3w, R (375 mg/m 2 ) len (20 mg) qd. primary endpoint was OS intent-to-treat population. Secondary endpoints were investigator-assessed progression-free (PFS), objective response rate (ORR), complete (CR) rate. preplanned IA performed at 134 events prespecified boundary of 2-sided P=0.0232. Results: 230 randomized: 112 to 118 R2; all but (both arm) ≥1 dose drug. Median age 71 yrs (range, 21-89), 56.5% male, 10.9% had ECOG 2. prior lines therapy 2-8); 29% 68% CD30- (<1% CD30 tumor expression). At median follow-up 16.4 months (mos) 0.1-31.5) (cut-off: January 22, 2024), 13.8 mos (95% CI: 10.3-18.8) 8.5 5.4-11.7) (HR 0.629; 95% 0.445-0.891; P=0.0085); benefit consistent across key subgroups. PFS 4.2 2.9-7.1) 2.6 1.4-3.1) 0.527; 0.380-0.729; P<0.0001). ORR 64.3% 54.7-73.1) 41.5% 32.5-51.0; P=0.0006); CR 40.2% 18.6%, respectively. In CD30+ subgroups, ORR/CR 72.2%/38.9% 60.5%/40.8% BV+R2, respectively, 50.0%/26.3% 37.5%/15.0% R2, Efficacy including cell origin will be presented. profile tolerable R2: Grade (Gr) ≥3 treatment-emergent adverse (TEAEs) 88% 77%, serious TEAEs 60% 50%, Gr 5 12% 8%, Most common neutropenia (46% 32%), anemia (29% 27%), diarrhea (31% 23%). Rates peripheral neuropathy 31% 24% (all Gr) 6% 2% (Gr 3). treatment duration 3.6 2.0 R2. Conclusions: Treatment triplet, demonstrated statistically significant clinically meaningful improvements outcomes high-risk manageable safety. This triplet regimen represents option Clinical trial information: NCT04404283 .