Ps1556 bruton tyrosine kinase inhibitor is an effective steroid-sparing agent in chronic graft-versus-host disease
HemaSphere(2019)
摘要
Background: Novel insights into the pathophysiology of GVHD highlighted the relevant role of the host inflammatory response governed by Bruton tyrosine kinase (BTK) signaling pathway. Ibrutinib is a first class, once daily inhibitor of BTK with proven efficacy in B cell lympho‐proliferative diseases, was recently employed in corticosteroid‐ refractory chronic GVHD with encouraging overall response rates(Miklos et all, Blood 2017). We previously reported the results of 14 patients who received ibrutinib treatment for steroid‐refractory cGVHD (Ilhan et all, ASH 2018) Aims: Herein, we share a real‐life experience using ibrutinib in the treatment of streoid‐refractory cGVHD in 30 patients from centers in Turkey. Methods: This multicenter retrospective study conducted in 9 stem cell transplant centers from Turkey included 30 adult patients diagnosed with steroid‐refractory cGVHD. We treated off‐label these patients from June 2017 to July 2018 with ibrutinib with a dose of 420 mg P.O. qday. Organ sites affected and cGVHD grading before starting ibrutinib were classified according to the National Institues of Health (NIH) 2014 criteria. Steroid refractory cGVHD was defined as any disease that failed to respond to previous immunosuppressive therapy with steroids at least 4 weeks or inability to taper it with or without additional immunosuppressive drugs. Results: The baseline characteristics of the patients are listed in Table 1. Patients had undergone both myeloablative and non‐myeloablative Allo‐SCT for a variety of underlying hematological malignancies. As expected mouth and skin were the most frequently involved organs and 56.7 % of patients showed evidence of cGVHD in more than 2 organs. The median Karnofsky Performance Status score was 65% (20%>100%). At a median follow‐up of 22.3 months (range, 7.1–109 months) after evidence of cGVHD showed, 27 (90%) patients were still receiving ibrutinib and 3 (10%) had discontinued treatment, because of cGVHD progression. Treatment duration ranged from 2 to 12 months (median 6 months) for all patients. Only three patients had grade 2 muscle spasm, arrhythmia and diarrhea as adverse events and need to reduce the 25% of drug dosage. No several adverse events due to ibrutinib were observed in our cohort. In the all treated population, the overall response rate (ORR), based on the 2005 NIH cGVHD Consensus Panel response criteria, was 63.3%, with a CR rate of 23.3 % and a PR rate of 40 %. For the responders, the median time to initial response was 28 days. Five patients had stable disease under the ibrutinib treatment and still continue receiving. Analysis by organ domain showed similar rates of response in the skin (91.7%), lung (85.7%) and mouth (80%). However the response in the liver (71.4%) was lower than the others. At the time of data collection, three patient had deceased. Summary/Conclusion: Based on the results of our study; the clinically meaningful response with safety profile observed with ibrutinib as a salvage therapy for chronic GVHD in accordance with Miklos and colleagues's report. However, in contrast to their results; patients with skin and lung manifestations of cGVHD were appeared to have somewhat better responses to ibrutinib than patients with cGVHD involving liver. It is important to note that prospective randomized controlled studies with large number of patients are warranted to find out the standard regimen for steroid‐refractory cGVHD. image
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关键词
tyrosine,inhibitor,steroid-sparing,graft-versus-host
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