Phase II Multicenter Study of Ofatumumab in Combination with Glucocorticoids As a Primary Therapy for Chronic Graft Versus Host Disease

Introduction B-cell homeostasis plays an important role in chronic GVHD (cGVHD). The safety and feasibility of anti-CD20 directed B-cell therapy with ofatumumab and glucocorticoids (GC) were previously established in a phase I trial. Methods A total of 38 adult patients (pts) with moderate/severe cGVHD were enrolled in phase II trial at 3 academic US centers (02/2014-08/2018). Ofatumumab was given at 1000 mg IV on days 0 and 14 of initial 1 mg/kg/day prednisone (or equivalent) therapy. Primary endpoint was the overall (complete and partial) response rate (ORR) at 6 months as reported by the physician (MD). Results Baseline data are summarized in Table. Six-month ORR for 32 evaluable pts was 62.5% (95%CI, 44-79%) by MD report (15.6% CR; 46.9% PR) and by NIH2014 criteria (9.4% CR; 53.1% PR) with good inter-rater reliability (Cohenu0027s kappa=0.73; discordant responses n=4). Given historical benchmark ORR of 60% at 6 months, the trial did not reach its primary endpoint (p=0.4) of 20% improvement with ofatumumab. Subsequent ORR per MD and NIH2014 were 42% and 31% at 12 months (kappa=0.6) and 36% and 32% at 24 months (kappa=0.9). GC discontinuation was successful in 45% and 54% of pts at 12 and 24 months (Figure 1A). Median follow up of survivors was 24 months (range, 0.7-46). Two-year OS and PFS were 74% and 72%. Failure-free survival (FFS) - composite outcome with death, relapse, and second-line immune suppression as events - was 53% at 12 months and 39% at 24 months. Second-line therapy was the most common failure event (13/22, Figure 1B). 14 non-fatal possibly related AEs occurred in 11 pts, including 5 SAEs in 3 pts. 17 infusion-related AEs (all ≤Gr2) occurred, but resolved with symptom management. Bacterial (13 events), fungal (8), and viral (26) infections were observed in 29%, 13%, and 40% of pts, respectively. 9 deaths occurred within 2 years, none of which was deemed related to study therapy. Conclusions This multicenter phase II trial did not demonstrate statistical difference in 6 month ORR with ofatumumab+GC vs. GC-based historical benchmark in the frontline therapy of cGVHD. Data on predictors of response, patient-reported outcomes, and immune reconstitution will be presented at the meeting.