A phase 2 multicenter trial of ofatumumab and prednisone as initial therapy for chronic graft-versus-host disease.

Abstract

Standard initial therapy of chronic graft vs. host disease (cGVHD) with glucocorticoids results in suboptimal response. Safety and feasibility of therapy with ofatumumab (1000 mg IV on days 0 and 14) and prednisone (1 mg/kg/day) was previously established in our phase I trial (n = 12). We now report the mature results of the phase II expansion of the trial (n = 38). The overall NIH severity of cGVHD was moderate (63%) or severe (37%) with 74% of all patients affected by the overlap subtype of cGVHD and 82% by prior acute cGVHD. The observed 6 month clinician-reported and 2014 NIH-defined overall response rates (ORR = complete + partial response [CR/PR]) of 62.5% (1-sided lower 90% confidence interval=51.5%) were not superior to pre-specified historic benchmark of 60%. Post-hoc comparison of 6 month NIH response suggested benefit compared to more contemporaneous NIH-based benchmark of 48.6% with frontline sirolimus/prednisone (CTN 0801 trial). Baseline cGVHD features (organ involvement, severity, initial immune suppression agents) were not significantly associated with 6-month ORR. The median time to initiation of second-line therapy was 5.4 months (range 0.9-15.1 months). Failure-free survival (FFS) was 64.2% (95% CI 46.5-77.4%) at 6 months and 53.1% (95% CI 35.8-67.7%) at 12 months, whereas FFS with CR/PR at 12 months of 33.5% exceeded a benchmark of 15% in post-hoc analysis, and was associated with greater success in steroid discontinuation by 24 months (odds ratio 8 (95% CI 1.21-52.7). This single-arm phase II trial demonstrated acceptable safety and potential efficacy of the upfront use of ofatumumab in combination with prednisone in cGVHD.  This trial was registered at www.clinicaltrials.gov as #NCT01680965.

• Authors: Aleksandr Lazaryan, Stephanie Lee, Mukta Arora, Jongphil Kim, Brian Christopher Betts, Farhad Khimani, Taiga Nishihori, Nelli Bejanyan, Hien Liu, Mohamed A Kharfan-Dabaja, Frederick L Locke, Rebecca Gonzalez, Michael D Jain, Marco L Davila, Lia Elena Perez, Asmita Mishra, Ariel Perez Perez, Karlie Balke, Ernesto Ayala, Leonel Ochoa, Omar Castaneda Puglianini, Rawan Faramand, Melissa Alsina, Hany Elmariah, Michael L Nieder, Hugo Fernandez, Claudio Anasetti, Joseph A Pidala
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 1 Pg. 259-269 (01 11 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 34649279 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• ofatumumab
• Prednisone

Topics

• Antibodies, Monoclonal, Humanized (therapeutic use)
• Drug Therapy, Combination (adverse effects)
• Graft vs Host Disease (drug therapy)
• Humans
• Immunosuppression Therapy
• Prednisone (therapeutic use)