A phase 2 multicenter trial of ofatumumab and prednisone as initial therapy for chronic graft-versus-host disease
Year: 2021
Type: article
Study design: Clinical Trial
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.
Source: Blood Advances
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
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funder: National Cancer Institute
OpenAlex ID: W3207935630