Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma

Author(s): Nancy L. Bartlett, MD¹, Uwe Hahn, MD², Won-Seog Kim, MD, PhD³, Isabelle Fleury, MD⁴, Kamel Laribi, MD⁵, Juan-Miguel Bergua, MD⁶, Krimo Bouabdallah, MD⁷, Nicholas Forward, MSc, MD, FRCPC⁸, Fontanet Bijou, MD⁹, David MacDonald, MD¹⁰, Craig A. Portell, MD¹¹, Herve Ghesquieres, MD, PhD¹², Grzegorz Nowakowski, MD¹³, Christopher A. Yasenchak, MD¹⁴, Monica Patterson, PharmD¹⁵, Linda Ho, MD¹⁵, Evelyn Rustia, MD¹⁵, Michelle Fanale, MD¹⁵, Fei Jie, PhD¹⁵, Jeong-A Kim, MD¹⁶;

Source: https://doi.org/10.1200/JCO-24-02242

Dr. Anjan Patel's Thoughts

The ECHELON-3 study showed BV + Len + R is an active and (relatively) tolerable in the rrDLBCL patient group. Interestingly, patients did not have to be CD30+ to see a benefit.

PURPOSE

In patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), brentuximab vedotin (BV) as monotherapy or combined with either lenalidomide (Len) or rituximab (R) has demonstrated efficacy with acceptable safety. We evaluated the efficacy and safety of BV + Len + R versus placebo + Len + R in patients with R/R DLBCL.

METHODS

ECHELON-3 is a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial comparing BV + Len + R with placebo + Len + R in patients with R/R DLBCL. Patients received BV or placebo once every 3 weeks, Len once daily, and R once every 3 weeks. The primary end point was overall survival (OS), and secondary end points included investigator-assessed progression-free survival (PFS) and objective response rate (ORR). A prespecified interim analysis was performed after 134 OS events, with two-sided P = .0232 as the efficacy boundary.

RESULTS

Patients (N = 230) were randomly assigned to receive BV + Len + R (n = 112) or placebo + Len + R (n = 118). Two patients in the placebo arm did not receive treatment. With a median follow-up of 16.4 months, the median OS was 13.8 months with BV + Len + R versus 8.5 months with placebo + Len + R (hazard ratio, 0.63 [95% CI, 0.45 to 0.89]; two-sided P = .009). The median PFS was 4.2 months with BV + Len + R versus 2.6 months with placebo + Len + R (hazard ratio, 0.53 [95% CI, 0.38 to 0.73]; two-sided P < .001). The ORR was 64% ([95% CI, 55 to 73]; two-sided P < .001) with BV + Len + R and 42% (95% CI, 33 to 51) with placebo + Len + R; complete response rates were 40% and 19%, respectively. Treatment-emergent adverse events (AEs) occurred in 97% of patients in both arms. In both arms, the most common treatment-emergent AEs were neutropenia, thrombocytopenia, diarrhea, and anemia.

CONCLUSION

BV + Len + R demonstrated a statistically significant survival benefit with a manageable safety profile in heavily pretreated patients with R/R DLBCL.

Author Affiliations

¹ Division of Oncology, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO; ² Haematology Unit, Royal Adelaide Hospital, Adelaide, Australia; ³ Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea; ⁴ Hôpital Maisonneuve-Rosemont, Institut Universitaire d’Hématologie-Oncologie et de Thérapie Cellulaire, Université de Montréal, Montréal, QC, Canada; ⁵ Department of Hematology, Centre Hospitalier Le Mans, Le Mans, France; ⁶ Hospital San Pedro de Alcantara, Cáceres, Spain; ⁷ Service d’Hematologie Clinique et Therapie Cellulaire, CHU Haut-Leveque, Pessac, France; ⁸ Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada; ⁹ Centre de Lutte Contre le Cancer (CLCC)—Institut Bergonié, Bordeaux, France; ¹⁰ Division of Hematology, The Ottawa Hospital, Ottawa, ON, Canada; ¹¹ UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, VA; ¹² Hematology Department, Hôpital Lyon Sud—HCL, Lyon, France; ¹³ Division of Hematology, Mayo Clinic, Rochester, MN; ¹⁴ Willamette Valley Cancer Institute and Research Center/US Oncology Research, Eugene, OR; ¹⁵ Pfizer Inc, Bothell, WA; ¹⁶ St Vincent’s Hospital, The Catholic University of Korea, Suwon, South Korea

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