Citations 1
A randomized phase 2 study of ipilimumab, nivolumab, and brentuximab vedotin in patients with relapsed Hodgkin lymphoma
Jegede, Opeyemi A. , Wang, Victoria, Ansell, Stephen M., Kostakoglu, Lale, Steidl, Christian , Natkunam, Yasodha , Scott, David W., Ambinder, Richard F, David, Kevin A. , Advani, Ranjana H, Bartlett, Nancy L., Thomas, Sachdev , Cohen, Jonathon B. , Goyal, Gaurav, Mehta-Shah, Neha, Amengual, Jennifer E. , Forlenza, Christopher Jon, Cole, Peter D. , Duan, Fenghai , Kelly, Kara M, Advani, Ranjana H. , Scott, David W. , Kostakoglu, Lale , Diefenbach, Catherine S , Jagede, Opeyemi A. , Kostakoglu, Lale , Steidl, Christian , Natkunam, Yasodha , Scott, David W , Ambinder, Richard F , David, Kevin , Bartlett, Nancy L , Thomas, Sachdev P , Cohen, Jonathon B , Goyal, Guarav , Mehta-Shah, Neha , Amengual, Jennifer E , Cole, Peter D , Advani, Ranjana H , Diefenbach, Catherine , Wang, Victoria , Ansell, Stephen M. , Ambinder, Richard F. , Bartlett, Nancy L. , Robertson, Michael J. , Ibrahimi, Sami , Goyal, Gaurav , Mehta–Shah, Neha , Forlenza, Christopher J. , Kelly, Kara M , Kahl, Brad S.
Blood | February 9, 2026 | Volume: 147 | Issue: 18 | Pages: 2041-2052
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.