Lazaryan A, Lee SJ, Arora M, et al. Phase 2 Multicenter Trial of Ofatumumab and Prednisone as Initial Therapy of Chronic Graft-vs-Host Disease. Blood Advances. 2021; (doi: 10.1182/bloodadvances.2021005552).
The results of a new multicenter study of combined ofatumumab and prednisone for initially treating chronic graft-versus-host-disease (cGVHD) indicate the protocol is safe and potentially effective. Many patients respond suboptimally to standard upfront cGVHD therapy using glucocorticoids. A preceding phase 1 trial demonstrated the safety and feasibility of anti-CD20 directed B-cell therapy with ofatumumab (1,000 mg I.V. on days 0 and 14) and prednisone (1 mg/kg/day). The phase 2 trial of 38 patients included moderate (63%) or severe (37%) National Institutes of Health (NIH) cGVHD severity, with the overlap subtype of cGVHD affecting 74% of patients and prior acute cGVHD in 82%. There was significant post-therapy B-cell depletion, with marginal recovery seen within the first year from initial treatment. The 6-month clinician-reported and 2014 NIH-defined overall response rate (ORR) of 62.5% was not superior to the pre-specified 60% historic benchmark. The 6-month ORR did not significantly correlate with baseline cGVHD features such as organ involvement, severity, and initial IS agents. The average time to commencement of second-line therapy was 5.4 months. At 6 months, the failure-free survival (FFS) rate was 64.2%, and that rate dropped to 53.1% at 12 months. FFS with complete and partial response at 12 months was 33.5% compared with a 15% benchmark in post-hoc analysis. This correlated with more effective steroid discontinuation by 2 years.