A randomized phase 2 study of ipilimumab, nivolumab, and brentuximab vedotin in patients with relapsed Hodgkin lymphoma
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: ABSTRACT: The phase 1/2 Intergroup study E4412 investigated checkpoint blockade with nivolumab (Nivo) and ipilimumab (Ipi) combined with the CD30 targeting antibody-drug conjugate brentuximab vedotin (BV) in relapsed/refractory classic Hodgkin lymphoma. A total of 147 patients aged ≥12 years were randomized between BV/Nivo and BV/Ipi/Nivo; 132 patients were included in the primary efficacy analysis. The complete response (CR) rate, was 64.7% (52.2, 75.9) for BV/Nivo and 70.3% (57.6, 81.1) for BV/Ipi/Nivo (1-sided P = .29). The median survival follow-up was 38.0 months (interquartile range, 32.6-48.1). Progression-free survival (PFS) did not significantly differ between the 2 arms (hazard ratio [HR], 0.78, confidence interval [CI], 0.39-1.57; 1-sided P = .24). Treatment-related grade 3+ toxicities in the adult cohort, excluding rash, were similar between both arms (38.5% BV/Nivo and 39.3% BV/Ipi/Nivo); there was a higher frequency of grade 3 rash with BV/Ipi/Nivo (24.6%) compared with BV/Nivo (9.2%). We compared PFS by stem cell transplantation (SCT) status in a planned before hoc comparison; 58 patients received SCT, and 36-month PFS (from SCT) was >90% for both arms. Sixty-six patients were progression free after the first scan and did not undergo SCT. The 36-month PFS was 73.0% (54.5, 85.0) for BV/Ipi/Nivo compared with 45.8% (26.3, 63.4) for BV/Nivo (HR, 0.45; CI, 0.19-1.08; 1-sided P = .03). The study did not meet its primary end point of superior CR rate for the triplet, but it supports the use of checkpoint antibody-drug conjugate induction prior to auto SCT, and there is an intriguing signal of disease control for patients wishing to defer or avoid SCT with the triplet of BV/Ipi/Nivo. This trial was registered at www.clinicaltrials.gov as NCT01896999.
Source: Blood
Authors: Catherine S. Diefenbach, Opeyemi Jegede, Victoria Wang, Stephen M. Ansell, Lale Kostakoglu, Christian Steidl, Yasodha Natkunam, David W. Scott, Richard F. Ambinder, Kevin A. David, Ranjana H. Advani, Nancy L. Bartlett, Michael A. Roberston, Sachdev P. Thomas, Jonathon Cohen, Sami Ibrahimi, Gaurav Goyal, Neha Mehta-Shah, Jennifer E. Amengual, Christopher J. Forlenza, Peter D. Cole, Fenghai Duan, Kara Kelly, Brad S. Kahl
Institutions: NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, Dana-Farber Cancer Institute, Mayo Clinic, University of Virginia Cancer Center, University of Virginia, University of British Columbia, Stanford Medicine, Stanford University, Johns Hopkins University, Rutgers Cancer Institute, Stanford Cancer Institute, Washington University in St. Louis, Indiana University Indianapolis, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Kaiser Permanente, Kaiser Permanente Vallejo Medical Center, Emory University, Winship Cancer Institute, University of Oklahoma Health Sciences Center, University of Alabama at Birmingham, UAB Medicine, Columbia University Irving Medical Center, Columbia University, Memorial Sloan Kettering Cancer Center, Brown University, Roswell Park Comprehensive Cancer Center, University at Buffalo, State University of New York
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Kaiser Permanente NCI National Community Oncology Research Program, NCORP, ECOG-ACRIN Network Group Operations Center, Network Lead Academic Participating Site Grant from the Roswell Park Cancer Institute, Network Lead Academic Participating Site: Memorial Sloan Kettering Cancer Center, SWOG Network Group Operations Center of the NCTN, Winship National Clinical Trials Network Lead Academic Participating Site, Canadian Cancer Trials Group - Canadian Collaborating Clinical Trials Network, NRG Oncology Network Group Operations Center, NCTN Deep South Research Consortium, Washington University/Siteman Cancer Center Lead Academic Site, NCI, National Clinical Trials Network Lead Academic Participating Site (LAPS) UG1, A Lead Academic Participating Site in Oklahoma for the Design and Conduct of NCTN Clinical Trials, ECOG-ACRIN Network Group Statistics and Data Management Center, Johns Hopkins University NCTN Lead Academic Site Program, Alliance for Clinical Trials in Oncology Operations Center, Cancer Center Support Grant
OpenAlex ID: W7128446411