Ibrutinib for therapy of steroid-refractory chronic graft vs. host disease: A multicenter real-world analysis.

To examine activity of ibrutinib in steroid-refractory chronic GVHD (SR-cGVHD) after FDA approval, we conducted a multicenter retrospective study. Data were standardly collected (N=270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), GI (26%), lung (27%), liver (19%), genital (7%), other (4.4%). NIH severity was mild in 5.7%, moderate 42%, severe 53%. 39% had overlap subtype. KPS was ≥ 80% in 72%. Median prednisone (mg/kg) was 0.21 (0-2.27). Ibrutinib was started at median of 18.2 months after cGVHD onset and in earlier lines of therapy (2nd line: 26%, 3rd: 30%, 4th: 21%, 5th: 9.6%, 6th: 10%, 7th or higher: 1.2%)). Among evaluable subjects, the 6 month NIH overall response rate (CR/PR) was 45% (PR 42%, CR 3%). Median duration of response was 15 months (range 1-46). Liver involvement had association with 6 month ORR (multivariate (MVA) OR 5.49 (95% CI 2.3-14.2, p <0.001). Best overall response was 56%, with most (86%) achieving by 1-3 months. With median follow up for survivors of 30.5 months, FFS was 59% (53-65%) at 6 months and 41% (36-48%) at 12 months. On MVA, increased age (HR 1.01, 95% CI 1.0-1.02, p=0.033), higher baseline prednisone (HR 1.92, 1.09-3.38, p=0.032), and lung involvement (HR 1.58, 1.1-2.28, p=0.016) had worse FFS. Ibrutinib discontinuation was most commonly due to progressive cGVHD (44%) or toxicity (42%). These data support that ibrutinib has activity in SR-cGVHD, provide new insight into factors associated with response and FFS, and demonstrate the toxicity profile associated with discontinuation.

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