A randomized phase 2 study of ipilimumab, nivolumab, and brentuximab vedotin in patients with relapsed Hodgkin lymphoma
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.
Article Details
Authors (24)
Catherine S. Diefenbach
1Perlmutter Cancer Center at NYU Langone Health, NYU Grossman School of Medicine, New York, NY
Opeyemi Jegede
2Department of Data Science, ECOG-ACRIN Biostatistical Center, Dana-Farber Cancer Institute, Boston, MA
Victoria Wang
Stephen M. Ansell
3Department of Hematology/Oncology, Mayo School of Graduate Medicine, Mayo Clinic, Rochester, MN
Lale Kostakoglu
4University of Virginia Cancer Center, Charlottesville, VA
Christian Steidl
5Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, Canada
Yasodha Natkunam
David W. Scott
5Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, Canada
Richard F. Ambinder
Kevin A. David
10Rutgers Cancer Institute, New Brunswick, NJ
Ranjana H. Advani
Nancy L. Bartlett
2Division of Oncology, Department of Medicine, Siteman Cancer Center, St Louis, MO
Michael A. Roberston
13Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN
Sachdev P. Thomas
14Department of Hematology/Oncology, Kaiser Permanente-Vallejo, Vallejo, CA
Jonathon Cohen
15Winship Cancer Institute, Emory University, Atlanta CA
Sami Ibrahimi
16Department of Hematology Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Gaurav Goyal
1Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL
Neha Mehta-Shah
3Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
Jennifer E. Amengual
Christopher J. Forlenza
19Department of Pediatric Hematology Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Peter D. Cole
Fenghai Duan
20ECOG-ACRIN Biostatistical Center, Brown University School of Public Health, Providence, RI
Kara Kelly
21Roswell Park Comprehensive Cancer Center, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY
Brad S. Kahl
30Division of Oncology, Washington University School of Medicine, St. Louis, MO