BRUTON TYROSINE KINASE INHIBITOR IS AN EFFECTIVE STEROID-SPARING AGENT IN CHRONIC GRAFT-VERSUS-HOST DISEASE
Author(s): ,
Osman Ilhan
Affiliations:
Hematology,Ankara University School of Medicine,Ankara,Turkey
,
Guldane Cengiz Seval
Affiliations:
Hematology,Ankara University School of Medicine,Ankara,Turkey
,
S. Sami Karti
Affiliations:
Hematology,Acıbadem Hospital,İstanbul,Turkey
,
Zafer Gulbas
Affiliations:
Hematology,Anadolu Medical Center,İstanbul,Turkey
,
Burak Deveci
Affiliations:
Hematology,Antalya Medstar Hospital,Antalya,Turkey
,
Zubeyde Nur Ozkurt
Affiliations:
Hematology,Gazi University School of Medicine,Ankara,Turkey
,
Ali Ugur Ural
Affiliations:
Hematology,Bayindir Hospital,Ankara,Turkey
,
Huseyin Saffet Bekoz
Affiliations:
Hematology,Medipol Mega Hospital,İstanbul,Turkey
,
Meltem Aylı
Affiliations:
Hematology,Gulhane Education and Research Hospital,Ankara,Turkey
,
Sevindik Omur Gokmen
Affiliations:
Hematology,Medipol University School of Medicine,Istanbul,Turkey
,
Irfan Yavasoglu
Affiliations:
Hematology,Adnan Menderes University School of Medicine,Aydin,Turkey
,
Sinem Civriz Bozdag
Affiliations:
Hematology,Ankara University School of Medicine,Ankara,Turkey
Meltem Kurt yüksel
Affiliations:
Hematology,Ankara University School of Medicine,Ankara,Turkey
EHA Library. Ilhan O. Jun 15, 2019; 267173; PS1556
Prof. Dr. Osman Ilhan
Prof. Dr. Osman Ilhan
Contributions
Abstract

Abstract: PS1556

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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.

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. 

Session topic: 22. Stem cell transplantation - Clinical

Keyword(s): Graft-versus-host disease (GVHD), Ibrutinib

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